Compositions and methods for therapeutic delivery with frozen particles

ABSTRACT

Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR THERAPEUTICDELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick A.Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-002-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR THERAPEUTICDELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick A.Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-002B-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR THERAPEUTICDELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick A.Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-002C-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR THERAPEUTICDELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick A.Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-002D-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR THERAPEUTICDELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick A.Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-002E-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR THERAPEUTICDELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick A.Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-002F-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 A-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 B-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 C-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 D-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 E-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 F-000000.

The present application is related to U.S. patent application Ser. No.to be assigned, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASIONWITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook, RoderickA. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney andLowell L. Wood, Jr. as inventors, filed 31 Oct. 2008, which is DocketNo. 0508-004-001 G-000000.

All subject matter of the Related Applications and of any and allparent, grandparent, great-grandparent, etc. applications of the RelatedApplications is incorporated herein by reference to the extent suchsubject matter is not inconsistent herewith.

SUMMARY

In at least one aspect, a therapeutic composition includes one or morefrozen particles including at least one therapeutic agent and at leastone of hydrogen oxide, helium, neon, krypton, argon, xenon, nitrogen,chlorine, bromine, oxygen, air, carbon dioxide, polyethylene glycol,acetone, ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether. In at leastone embodiment, at least one of the constituents of the one or morefrozen particles is frozen. In at least one embodiment, all of theconstituents of the one or more frozen particles are frozen. In at leastone embodiment, the at least one composition or therapeutic compositionincludes one or more frozen solution particles. In at least oneembodiment, the composition or therapeutic composition includes one ormore frozen solution particles and the composition or therapeuticcomposition is in at least one crystalline or amorphous phase. In atleast one embodiment, the frozen solution particles include at least oneof the constituents described herein.

In at least one embodiment, the at least one composition or therapeuticcomposition includes hydrogen oxide in the form of at least one ofamorphous frozen water, low density amorphous ice, high densityamorphous ice, crystalline ice, very high density amorphous ice,clathrate ice, or hyperquenched glassy water. In at least oneembodiment, the one or more frozen particles include hydrogen oxide inthe form of at least one of ice Ic, ice Ih, ice II, ice III, ice IV, iceV, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice XII, ice XIII,or ice XIV. In at least one embodiment, the one or more frozen particlesinclude hydrogen oxide in the form of ice Ic.

In at least one embodiment, the one or more frozen particles have atleast one major dimension of approximately one decimeter or less,approximately one centimeter or less, approximately one millimeter orless, approximately one micrometer or less, approximately one nanometeror less, approximately one picometer or less, or any value therebetween.In at least one embodiment, the one or more frozen particles have atleast one major dimension of approximately ten micrometers or less. Inat least one embodiment, the at least one major dimension of the one ormore frozen particles includes at least one of radius, diameter, length,width, height, or perimeter of a particle. In at least one embodiment,the one or more frozen particles have a density greater thanapproximately 0.92 g/cm³.

In at least on embodiment, the one or more frozen particles approximatethe shape of at least one of a sphere, bullet, flechette, cone, needle,arrow, spear, diamond, pyramid, cylinder, minie ball, shuttlecock,spiral, bell, pear, crystal, cube, spheroid, tetrahedron, crescent, orhigh aspect ratio shape. In at least one embodiment, the one or morefrozen particles include a plurality of frozen particles that areapproximately uniform with regard to size, shape, weight, or density.

In at least one embodiment, the one or more frozen particles or thecompositions exist at about 30° C., about 20° C., about 10° C., about 5°C., about 0° C., about −10° C. about −20° C., about −30° C., about −40°C., about −50° C., about −60° C., about −70° C., about −75° C., about−80° C., about −85° C., about −90° C., about −95° C., about −100° C.,about −120° C., about −150° C., about −180° C., about −200° C., about−220° C., about −250° C., or any value less therebetween. In certaininstances, the one or more frozen particles are utilized at a very coldtemperature so that effective penetration of a biological tissue isachieved. In certain instances, the one or more frozen particles areutilized at warmer temperatures, particularly if the contents of the oneor more frozen particles include agents that have warmer freezingtemperatures. For example, the freezing point of nitrogen isapproximately −210° C., whereas the freezing point of dimethyl sulfoxide(DMSO) is approximately 18.45° C. Thus, frozen particles of DMSO can beutilized or administered at a warmer temperature than frozen particlesof nitrogen.

In at least one embodiment, the composition or therapeutic compositionincludes at least one of a polymer, biopolymer, nanoparticle, ordetection material. In certain instances, the detection material may belocated on or in the one or more frozen particles. In certain instances,the detection material may be intermixed with the one or more frozenparticles. In certain instances, the detection material provides a“tracer” agent that allows for viewing one or more locations ofadministration of the at least one composition or therapeuticcomposition. Thus, in certain instances the detection material islocated on the at least one therapeutic composition or the at least onefrozen particle. In other instances, the detection material is separatefrom the at least one therapeutic composition or the at least one frozenparticle and forms a mixture with the therapeutic composition or frozenparticles or is administered at approximately the same time, inapproximately the same place, or in approximately the same manner as theone or more therapeutic compositions or frozen particles.

In at least one embodiment, the detection material includes at least oneelectronic identification device. In at least one embodiment, the atleast one electronic identification device includes at least one radiofrequency identification device. In at least one embodiment, thedetection material includes at least one radioactive element. In atleast one embodiment, the radioactive element includes one or more of³²P, ³⁵S, ¹³C, ¹³¹I, ¹⁹¹Ir, ¹⁹²Ir, ¹⁹³Ir, ²⁰¹Tl, or ³H.

In at least one embodiment, the detection material includes at least onecolorimetric substance. In at least one embodiment, the at least onecolorimetric substance includes one or more of an inorganic, organic,biological, natural, artificial, or synthetic substance. In at least oneembodiment, the at least one calorimetric substance includes one or moreof a dye, pigment, or a light-emitting substance. In at least oneembodiment, the light-emitting substance includes at least one of aluminescent substance, fluorescent substance, phosphorescent substance,or quantum dot. In at least one embodiment, the at least onecalorimetric substance is biocompatible.

In at least one embodiment, the detection material includes at least oneof a diamagnetic particle, ferromagnetic particle, paramagneticparticle, super paramagnetic contrast agent, or other magnetic particle.

In at least one embodiment, the composition or therapeutic compositionincludes one or more abrasives, one or more reinforcement agents, or oneor more explosive materials. In at least one embodiment, the one or moreexplosive materials include at least one of a high explosive or a lowexplosive. In at least one embodiment, the one or more explosivematerials include at least one of carbon dioxide, nitroglycerine, or areactive metal.

In at least one embodiment, the one or more reinforcement agents includeat least one of a natural, artificial, or synthetic agent. In at leastone embodiment, the one or more reinforcement agents include at leastone of a plate, fiber, or spheroid. In at least one embodiment, the oneor more reinforcement agents include one or more of polyaramid,vinylester matrix, metal, ceramic, fiberglass, cellulose, broad carbide,aromatic polyamide, nylon, silk, rayon, acetate, modacrylic, olefin,acrylic, polyester, aromatic polyester, poly-lactic acid, vinyon, saran,spandex, vinalon, aromatic nylon, vinylidene chloride, modal,polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performancepolyethylene, polypyridobenzimidazole, vectran, acrylonitrile rubber,glass, copper, iron, steel, sodium, potassium, calcium, zinc, manganese,carbon, magnesium, silicon, silica, hydrogen oxide ice, plant matter(including vegetable matter), animal matter, or mineral matter. In atleast one embodiment, the one or more reinforcement agents are locatedat least on the surface or beneath the surface of the particle. In atleast one embodiment, the one or more reinforcement agents are locatedwithin the particle.

In at least one embodiment, the at least one therapeutic agent includesat least one of an organic or inorganic small molecule, clathrate orcaged compound, protocell, coacervate, microsphere, proteinoid,laminate, helical rod, liposome, macroscopic tube, noisome, sphingosome,toroid, vesicular tube, vesicle, small unilamellar vesicle, largeunilamellar vesicle, large multilamellar vesicle, multivesicularvesicle, lipid layer, lipid bilayer, micelle, organelle, cell, membrane,nucleic acid, peptide, polypeptide, protein, glycopeptide, glycolipid,sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan, lipid,carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus, acid,base, buffer, protic solvent, aprotic solvent, nitric oxide, nitricoxide synthase, amino acid, micelle, polymer, co-polymer, or piloxymer.

In at least one embodiment, the at least one therapeutic agent includesat least one of an anti-tumor agent, antimicrobial agent, anti-viralagent, analgesic, antiseptic, anesthetic, diagnostic agent,anti-inflammatory agent, vaccine, cell growth inhibitor, cell growthpromoter, immunogen, antigen, radioactive agent, apoptotic promotingfactor, angiogenic factor, anti-angiogenic factor, hormone, vitamin,mineral, nutraceutical, cytokine, chemokine, probiotic, coagulant,anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer,smooth muscle cell activator, epinephrine, adrenaline, neurotoxin,neuro-muscular toxin, Botulinum toxin type A, microbial cell orcomponent thereof, or virus or component thereof.

In at least one embodiment, the antimicrobial agent includes at leastone of an anti-fungal agent, antibiotic agent, anti-parasitic agent, oranti-worm agent. In at least one embodiment, the at least one anti-tumoragent includes one or more of an alkylating agent, antimetabolite,anthracycline, plant alkaloid, topoisomerase inhibitor, monoclonalantibody, or tyrosine kinase inhibitor. In at least one embodiment, theat least one plant alkaloid includes paclitaxel.

In at least one embodiment, the at least one therapeutic agent includesone or more of a prodrug or precursor compound. In at least oneembodiment, the at least one therapeutic agent is activated by deliveryof the therapeutic composition to at least one biological tissue.

In at least one embodiment, the at least one therapeutic agent residesin one or more distinct regions of the one or more frozen particles. Inat least one embodiment, the one or more frozen particles include aplurality of frozen particles that are approximately uniform in size,shape, weight, or density.

In at least one embodiment, a therapeutic composition includes at leastone of a solid, liquid, or gas. In at least one embodiment, thetherapeutic composition includes one or more of a suspension, mixture,solution, sol, clathrate, colloid, emulsion, microemulsion, aerosol,ointment, capsule, powder, tablet, suppository, cream, device, paste,liniment, lotion, ampule, elixir, spray, suspension, syrup, tincture,detection material, polymer, biopolymer, buffer, adjuvant, diluent,lubricant, disintegration agent, suspending agent, solvent, colorimetricagent, light-emitting substance, glidant, anti-adherent, anti-staticagent, surfactant, plasticizer, emulsifying agent, flavor, gum,sweetener, coating, binder, filler, compression aid, encapsulation aid,preservative, granulation agent, spheronization agent, stabilizer,adhesive, pigment, sorbent, nanoparticle, or gel.

In at least one embodiment, the composition is formulated to be atherapeutic composition administered by one or more of topical delivery,oral delivery, enteral delivery, mucosal delivery, percutaneousdelivery, or parenteral delivery. In at least one embodiment, parenteraldelivery includes at least one of intravenous delivery, intra-arterialdelivery, intracardiac delivery, subcutaneous delivery, intraperitonealdelivery, or intramuscular delivery. In at least one embodiment, thecomposition or therapeutic composition is formulated to be administeredby high velocity impact. In at least one embodiment, the composition ortherapeutic composition is formulated to be administered by one or moredevices. In certain instances, an example of a device that may be usedfor administering one or more of the compositions described hereinincludes a handheld device, such as a wand, a pen, a baton, a hose, asprayer, a gun (e.g., a pellet gun), or other handheld device. Incertain instances, the device is at least part of a built-in deliverydevice, such as may be included in a wall, an overhead device, a corral,a gate, or a device that includes a cavity into which a subject may beplaced for administration or delivery of at least one compositiondescribed herein. In certain instances, the device has robotic action.In any of these instances, the device may be remotely controlled, forexample, by a human or computer program.

In at least one aspect, a method of providing at least one therapeuticagent to at least one biological tissue of a subject includes deliveringat least one therapeutic composition as described herein. In at leastone embodiment, delivering at least one therapeutic composition to atleast one biological tissue includes propelling the therapeuticcomposition toward the at least one biological tissue. In certaininstances, the therapeutic composition is propelled to or at apredetermined pressure for delivery of the at least one therapeuticcomposition to a desired location on or in the at least one biologicaltissue. In at least one embodiment, the therapeutic composition ispropelled using a pressure set at least about 10 psi, about 20 psi,about 30 psi, about 40 psi, about 50 psi, at least about 100 psi, atleast about 200 psi, at least about 300 psi, at least about 400 psi, atleast about 450 psi, at least about 500 psi, at least about 600 psi, atleast about 700 psi, at least about 800 psi, at least about 900 psi, atleast about 1000 psi, at least about 1100 psi, at least about 1200 psi,at least about 1300 psi, at least about 1400 psi, at least about 1500psi, about 2000 psi, about 2500 psi, about 3000 psi, about 3500 psi,about 4000 psi, about 5000 psi, about 6000 psi, about 7000 psi, about8000 psi, about 9000 psi, about 10000 psi, or any value therebetween.

In at least one embodiment, the at least one therapeutic composition ispropelled at or to a predetermined velocity for delivery of the at leastone therapeutic composition to a desired location of the at least onebiological tissue. In at least one embodiment, the at least onetherapeutic composition is propelled at or to a velocity ofapproximately 10 m/s, approximately 20 m/s, approximately 30 m/s,approximately 40 m/s, approximately 50 m/s, approximately 60 m/s,approximately 70 m/s, approximately 80 m/s, approximately 90 m/s,approximately 100 m/s, approximately 200 m/s, approximately 300 m/s,approximately 400 m/s, approximately 500 m/s, approximately 600 m/s,approximately 700 m/s, approximately 800 m/s, approximately 900 m/s,approximately 1000 m/s, approximately 1500 m/s, approximately 2000 m/s,or any value greater or therebetween.

In at least one embodiment, delivering at least one therapeutic agent toat least one biological tissue of a subject includes ejecting thetherapeutic composition toward at least one biological tissue. In atleast one embodiment, delivering at least one therapeutic compositionincludes accelerating the therapeutic composition toward at least onebiological tissue. In at least one embodiment, the at least onetherapeutic composition is accelerated to a predetermined velocity fordelivery of the at least one therapeutic composition to a desiredlocation of the at least one biological tissue. In at least oneembodiment, the at least one therapeutic composition is acceleratedtoward the at least one biological tissue to a velocity of approximately10 m/s, approximately 20 m/s, approximately 30 m/s, approximately 40m/s, approximately 50 m/s, approximately 60 m/s, approximately 70 m/s,approximately 80 m/s, approximately 90 m/s, approximately 100 m/s,approximately 200 m/s, approximately 300 m/s, approximately 400 m/s,approximately 500 m/s, approximately 600 m/s, approximately 700 m/s,approximately 800 m/s, approximately 900 m/s, approximately 1000 m/s,approximately 1500 m/s, approximately 2000 m/s, or any value greater ortherebetween.

In at least one embodiment, a method of providing at least onetherapeutic agent to at least one biological tissue includes propelling,ejecting, or accelerating multiple therapeutic compositions toward atleast one biological tissue. In at least one embodiment, a method ofproviding at least one therapeutic agent to at least one biologicaltissue includes delivering at least one therapeutic agent to at leastone biological tissue by propelling, ejecting, or accelerating two ormore of the multiple therapeutic compositions. In at least oneembodiment, the multiple therapeutic compositions include one or moresimilar therapeutic agents. In at least one embodiment, the multipletherapeutic compositions include one or more dissimilar therapeuticagents.

A particular plurality of compositions or therapeutic compositions mayinclude multiple frozen particles where various multiple agents areassociated with a single particle. Likewise, a particular plurality ofcompositions or therapeutic compositions may include various multipleagents, where each individual agent is associated with a single frozenparticle. In at least one embodiment, a plurality of compositions ortherapeutic compositions may include any number of subsets of frozenparticles associated with a particular therapeutic agent or otherconstituent. During the course of any particular method describedherein, one or more plurality of compositions or therapeuticcompositions, or any particular subset thereof, may be administered in asingle treatment.

One non-limiting example of multiple therapeutic agents capable ofcombining to form another therapeutic agent includes combining at leastone prodrug and at least one enzyme with a single frozen particle,wherein the at least one prodrug and at least one enzyme combine duringadministration to form at least one active therapeutic agent. In anothernon-limiting example, a single frozen particle includes at least oneadjuvant and at least one immunogen.

In at least one embodiment, delivering or administering the at least onecomposition or therapeutic composition includes contacting the at leastone surface of at least one biological tissue of a subject with at leastone composition or therapeutic composition. In at least one embodiment,delivering or administering the at least one composition or therapeuticcomposition includes contacting the at least one surface of at least onebiological tissue of a subject with one or more frozen particles. In atleast one embodiment, delivering or administering the at least onecomposition or therapeutic composition includes rupturing one or morecells of at least one surface of at least one biological tissue of asubject. In at least one embodiment, delivering the at least onetherapeutic composition occurs prior to, during, or subsequent tosurgery on the at least one biological tissue or on the subject.

In at least one embodiment, a method for providing at least onetherapeutic agent to at least one biological tissue includes at leastone biological tissue located in at least one of in situ, in vitro, invivo, in utero, in planta, in silico, or ex vivo. In certain instances,the at least one biological tissue includes at least one tissue or organthat was artificially synthesized from biological or other sources. Inat least one embodiment, the at least one biological tissue is locatedin vivo. In at least one embodiment, the at least one biological tissueis located in at least one tissue or organ related to transplantation.In at least one embodiment, the at least one tissue or organ related totransplantation includes at least one donor or recipient tissue ororgan. In at least one embodiment, the at least one donor includes atleast one cadaver. In at least one embodiment, the at least onebiological tissue is ingested by at least one subject. In at least oneembodiment, the at least one biological tissue includes one or more ofskin, scalp, hair, nail, nail bed, teeth, eye, ear, ovary, oviduct,tongue, tonsil, adenoid, liver, bone, pancreas, stomach, blood vessel,blood, lymph, heart, lung, brain, breast, kidney, bladder, urethra,ureter, gall bladder, uterus, prostate, testes, fallopian tubes, vasdeferens, large intestine, small intestine, esophagus, oral cavity,nasal cavity, otic cavity, connective tissue, muscle tissue, or adiposetissue. In at least one embodiment, methods and compositions describedherein relate to providing or removing reproductive sterilization of asubject.

In at least one embodiment, a method for abrasion of at least onebiological tissue surface of a subject and the at least one biologicaltissue includes at least one cell mass. In at least one embodiment, theat least one cell mass includes at least one of a scar, pore, pit,eschar, granuloma, keloid, artheromatous plaque, abscess, pustule,scaling (e.g., psoriasis or eczema), infected tissue, hair follicle,necrotic tissue, stratum corneum, wrinkle, wound, tumor, skin structure,nevus, cyst, lesion, callus, neoplastic tissue, gangrenous tissue, orcellular deposit.

In at least one embodiment, the at least one cell mass includes at leastone benign or malignant tumor. In at least one embodiment, the at leastone benign or malignant tumor relates to one or more of a melanoma,lymphoma, leukemia, sarcoma, blastoma, or carcinoma. In at least oneembodiment, the at least one cell mass is related to at least one bloodclot, microorganism accumulation, blood vessel obstruction, ductobstruction, bowel obstruction, infection, gangrene, connective tissuedestruction, tissue or organ damage, injury, white blood cellaccumulation, or cancer.

In at least one embodiment, a method includes delivering at least onetherapeutic agent to at least one biological tissue and includesdelivering to the at least one biological tissue at least one of apolymer, biopolymer, nanoparticle, or detection material, examples ofeach of which are described herein. In at least one embodiment, thedetection material is intermixed with the at least one therapeuticcomposition. In at least one embodiment, the detection material residesin the at least one therapeutic composition. In at least one embodiment,the detection material resides in the one or more frozen particles.

In at least one embodiment, a method includes delivering at least onetherapeutic agent to at least one biological tissue and the at least onebiological tissue is located at least one subject that includes at leastone invertebrate or vertebrate animal. In at least one embodiment, theat least one subject includes insects, insect cells, bacteria, algae,plankton, or protozoa. In at least one embodiment, the subject includesat least one insect, arachnid, microorganism, reptile, mammal,amphibian, bird or fish. In at least one embodiment, the subjectincludes at least one human. In at least one embodiment, the subjectincludes at least one livestock, pet, undomesticated herd animal, wildanimal or product animal. In at least one embodiment, the subjectincludes at least one of a sheep, goat, frog, dog, cat, rat, mouse,vermin, monkey, duck, horse, cow, pig, chicken, shellfish, fish, turkey,llama, alpaca, bison, wolf, fox, coyote, deer, rabbit, guinea pig, yak,chinchilla, mink, reindeer, deer, elk, raccoon, camel, donkey, or mule.

In at least one aspect, a method of vaccinating a subject includesdelivering or administering to a subject at least one therapeuticcomposition that includes at least one vaccine and one or more frozenparticles, examples of which are described herein.

In at least one embodiment, the at least one therapeutic compositionincludes at least one pharmaceutically-acceptable carrier or excipient.In at least one embodiment, the at least one vaccine includes at leastone prophylactic or therapeutic vaccine. In at least one embodiment, thetherapeutic vaccine includes an anti-cancer vaccine. In at least oneembodiment, the at least one therapeutic composition includes at leastone of an anti-tumor agent, antimicrobial agent, anti-viral agent,immunogen, antigen, live microbe, dead microbe, attenuated microbe,microbe or component thereof, live virus, recombinant virus, killedvirus, attenuated virus, virus component, plasmid DNA, nucleic acid,amino acid, peptide, protein, glycopeptide, proteoglycan, glycoprotein,glycolipid, sphingolipid, glycosphingolipid, cancer cell or componentthereof, organic or inorganic small molecule, or toxoid.

In at least one embodiment, the therapeutic composition includes atleast one adjuvant. In certain instances, the at least one adjuvantincludes one or more organic or inorganic compounds. In certaininstances, the at least one adjuvant includes at least one of aliposome, virosome, lipid, phospholipid, mineral salt, single-strandedDNA, double-stranded RNA, lipopolysaccharide, molecular antigen cage,CpG motif, microbial cell wall or component thereof, squalene, oilemulsion, surfactant, saponin, isolated microbial toxin, modifiedmicrobial toxin, endogenous immunomodulator, or cytokine.

In at least one embodiment, the method of vaccinating a subject includesdelivering the at least one therapeutic composition to at least onebiological tissue of the subject, examples of which are describedherein. For example, as described herein for any composition ortherapeutic composition, a vaccine composition may be propelled,accelerated, or ejected toward the at least one biological tissue. Incertain instances, delivering the at least one vaccine compositionincludes contacting the at least one biological tissue with the at leastone composition, therapeutic agent, or vaccine.

In at least one embodiment, a method of vaccinating a subject includesdelivering the at least one vaccine composition prior to, during, orsubsequent to surgery. In at least one embodiment, the at least onebiological tissue is located in at least one of in situ, in vitro, invivo, in utero, in planta, in silico, or ex vivo. In at least oneembodiment, the at least one biological tissue is located in vivo. In atleast one embodiment, the at least one biological tissue is transplantedor implanted into at least one subject. In at least one embodiment, thebiological tissue includes artificial or synthetic tissue or organs. Inat least one embodiment, the at least one biological tissue is ingestedby at least one subject. In at least one embodiment, the at least onebiological tissue includes at least one biological tissue from at leastone donor or recipient. In at least one embodiment, at least one donorincludes at least one cadaver.

In at least one embodiment, the at least one biological tissue includesone or more of skin, scalp, hair, nail, nail bed, teeth, eye, ear,ovary, oviduct, tongue, tonsil, adenoid, liver, bone, pancreas, stomach,blood vessel, blood, lymph, heart, lung, brain, breast, kidney, bladder,urethra, ureter, gall bladder, uterus, prostate, large intestine, smallintestine, esophagus, oral cavity, nasal cavity, otic cavity, connectivetissue, muscle tissue, or adipose tissue.

In at least one embodiment, a method of vaccinating a subject includesdelivering at least one vaccine composition to at least one biologicaltissue that includes at least one cell mass. In at least one embodiment,the at least one cell mass includes at least one of a scar, pore, pit,eschar, granuloma, keloid, artheromatous plaque, abscess, pustule, hairfollicle, necrotic tissue, stratum corneum, wrinkle, wound, tumor, skinstructure, nevus, cyst, lesion, callus, neoplastic tissue, gangrenoustissue, or cellular deposit. In at least one embodiment, the at leastone cell mass includes at least one benign or malignant tumor. In atleast one embodiment, the at least one benign or malignant tumor relatesto one or more of a melanoma, lymphoma, leukemia, sarcoma, blastoma, orcarcinoma. In at least one embodiment, the at least one cell mass isrelated to at least one blood clot, microorganism accumulation, bloodvessel obstruction, duct obstruction, bowel obstruction, infection,gangrene, connective tissue destruction, tissue or organ damage, injury,white blood cell accumulation, or cancer.

In at least one embodiment, a method of vaccinating a subject includesdelivering to the at least one biological tissue at least one of apolymer, biopolymer, nanoparticle, or detection material, examples ofeach of which are described herein.

In at least one embodiment, a method of vaccinating a subject includesadministering at least one vaccine composition to at least one subject,including at least one invertebrate or vertebrate animal. In at leastone embodiment, the subject includes insects, insect cells, bacteria,algae, plankton, or protozoa. In at least one embodiment, the subjectincludes at least one insect, arachnid, microorganism, reptile, mammal,amphibian, bird or fish. In at least one embodiment, the subjectincludes at least one human. In at least one embodiment, the subjectincludes at least one livestock, pet, undomesticated herd animal, wildanimal or product animal. In at least one embodiment, the subjectincludes at least one of a sheep, goat, frog, dog, cat, rat, mouse,vermin, monkey, duck, horse, cow, pig, chicken, shellfish, fish, turkey,llama, alpaca, bison, wolf, fox, coyote, deer, rabbit, guinea pig, yak,chinchilla, mink, reindeer, deer, elk, raccoon, camel, donkey, or mule.

In at least one aspect, a method includes comparing informationregarding at least one aspect of administering at least one frozenparticle therapeutic composition to at least one subject and informationregarding at least one clinical outcome following receipt by the atleast one subject of at least one frozen particle therapeuticcomposition; and providing output information that is optionally basedon the comparison.

In at least one embodiment, the method further comprises determining atleast one statistical correlation. In at least one embodiment, themethod further comprises counting the occurrence of at least oneclinical outcome or determining at least one correlation before theadministration of the at least one frozen particle therapeuticcomposition. In at least one embodiment, the information regarding theat least one aspect of administering at least one frozen particletherapeutic composition and the regarding at least one clinical outcomebefore the administration of the at least one frozen particletherapeutic composition to another subject. In at least one embodiment,the information regarding the at least one aspect of administering atleast one frozen particle therapeutic composition includes informationregarding the amount of at least one frozen particle therapeuticcomposition or therapeutic agent delivered or administered to at leastone biological tissue of a subject.

In at least one embodiment, the information regarding the at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information regarding at least one dimension ofbiological tissue penetration. In at least one embodiment, theinformation regarding the at least one dimension of biological tissuepenetration includes information regarding at least one of depth, width,or breadth of delivery or administration of at least one frozen particletherapeutic composition to at least one biological tissue of at leastone subject.

In at least one embodiment, the information regarding at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information regarding two or more subjects with oneor more common attributes. In at least one embodiment, the one or morecommon attributes include genetic attributes, mental attributes, orpsychological attributes. In at least one embodiment, the one or morecommon attributes include genotype attributes or phenotype attributes.

In at least one embodiment, the one or more common attributes include atleast one of height; weight; medical diagnosis; familial background;results on one or more medical tests; ethnic background; body massindex; age; presence or absence of at least one disease or condition;species; ethnicity; race; allergies; gender; thickness of epidermis;thickness of dermis; thickness of stratum corneum; keratin deposition;collagen deposition; blood vessel condition; skin condition; hair or furcondition; muscle condition; tissue condition; organ condition; nervecondition; brain condition; presence or absence of at least onebiological, chemical, or therapeutic agent in the subject; pregnancystatus; lactation status; genetic profile; proteomic profile; partial orwhole genetic sequence; partial or whole proteomic sequence; medicalhistory; or blood condition.

In the at least one embodiment, the output information includes at leastone of a response signal, a comparison code, a comparison plot, adiagnostic code, a treatment code, a test code, a code indicative of atleast one treatment received, a code indicative of at least oneprescribed treatment step, a code indicative of at least one vaccinationdelivered; a code indicative of at least one therapeutic agentdelivered; a code indicative of at least one diagnostic agent delivered;a code indicative of at least one interaction of a delivered agent andat least one biological or chemical agent in the subject; a codeindicative of at least one dispersion or location of at least onedelivered agent; a code indicative of at least one detection materialdelivered; a code indicative of the depth of penetration of a deliveredagent; or a code indicative of the condition of at least one location ofan administered frozen particle composition.

In at least one embodiment, the information regarding at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information regarding at least one cellular ortissue source. In at least one embodiment, the information regarding atleast one cellular or tissue source includes information regarding atleast one abnormal cellular or tissue source. In at least oneembodiment, the information regarding at least one cellular or tissuesource includes information regarding at least one type of cell ortissue.

In at least one embodiment, the at least one frozen particle therapeuticcomposition includes at least one of nitrogen, carbon dioxide, hydrogenoxide, helium, neon, xenon, krypton, air, oxygen, chlorine, oxygen, air,bromine, argon, polyethylene glycol, acetone, ethyl acetate, dimethylsulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether.

In at least one embodiment, the at least one frozen particle compositionincludes at least one major dimension of approximately one centimeter orless, approximately one millimeter or less, approximately one micrometeror less, approximately one nanometer or less, or any value therebetween.In at least one embodiment, the at least one frozen particle therapeuticcomposition includes one or more reinforcement agents, one or moreabrasives, or one or more explosive materials.

In at least one embodiment, the receipt by the at least one subject ofat least one frozen particle therapeutic composition is pursuant to atleast one clinical trial. In at least one embodiment, the methodincludes creating at least one inclusion criterion and at least oneexclusion criterion for a clinical trial involving the at least onefrozen particle therapeutic composition.

In at least one embodiment, the method further comprises suggesting theinclusion of one or more of the at least one subject in at least oneclinical trial. In at least one embodiment, the method further comprisessuggesting the exclusion of one or more of the at least one subject inat least one clinical trial. In at least one embodiment, the methodincludes using one or more of the at least one comparisons to predict atleast one clinical outcome regarding at least one second subject. In atleast one embodiment, the at least one second subject has not receivedthe at least one frozen particle therapeutic composition. In at leastone embodiment, using one or more of the at least one correlationfurther comprises predicting at least one clinical outcome involving theat least one second subject, wherein the at least one second subject isa plurality of people; and segregating subject identifiers associatedwith the plurality of people in reference to the predicted at least oneclinical outcome. In at least one embodiment, the method includesdetermining the eligibility of the at least one second subject for theat least one clinical trial.

In at least one aspect, a method of predicting a clinical outcome ofadministering at least one frozen particle therapeutic composition to atleast one biological tissue of at least one first subject includesdetermining a similarity or dissimilarity in information regarding atleast one aspect of administering at least one therapeutic compositionto the at least one biological tissue of the at least one first subjectto information regarding at least one aspect of administering at leastone therapeutic composition to the at least one biological tissue of theat least one second subject, wherein the at least one second subjectattained a clinical outcome following receipt of the at least one frozenparticle therapeutic composition; and providing output information,optionally based on the comparison or determination.

In at least one embodiment, the information regarding at least oneaspect of administering at least one therapeutic composition includesinformation regarding amount of at least one therapeutic composition ortherapeutic agent administered to at least one biological tissue of atleast one subject.

In at least one embodiment, the information regarding at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information regarding at least one dimension ofbiological tissue penetration. Such information may include, but not belimited to information regarding at least one of depth, width, orbreadth of administration of at least one frozen particle therapeuticcomposition to at least one biological tissue of at least one subject.In at least one embodiment, the information regarding at least oneaspect of administering at least one therapeutic composition includesinformation regarding two or more subjects with one or more commonattributes, including but not limited to genetic attributes, mentalattributes, or psychological attributes. In at least one embodiment, theone or more common attributes include genotype attributes or phenotypeattributes. In at least one embodiment, the one or more commonattributes include at least one of height; weight; medical diagnosis;familial background; results on one or more medical tests; ethnicbackground; body mass index; age; presence or absence of at least onedisease or condition; species; ethnicity; race; allergies; gender;thickness of epidermis; thickness of dermis; thickness of stratumcorneum; keratin deposition; collagen deposition; blood condition; lymphcondition; blood vessel condition; skin condition; hair or furcondition; muscle condition; tissue condition; organ condition; nervecondition; brain condition; presence or absence of at least onebiological, chemical, or therapeutic agent in the subject; pregnancystatus; lactation status; genetic profile; proteomic profile; partial orwhole genetic sequence; partial or whole proteomic sequence; medicalhistory; or blood condition.

In at least one embodiment, the output information includes at least oneof a response signal, a comparison code, a comparison plot, a diagnosticcode, a treatment code, a test code, a code indicative of at least onetreatment received, a code indicative of at least one prescribedtreatment step, a code indicative of at least one vaccinationadministered; a code indicative of at least one therapeutic agentadministered; a code indicative of at least one diagnostic agentadministered; a code indicative of at least one interaction of aadministered agent and at least one biological or chemical agent in thesubject; a code indicative of at least one dispersion or location of atleast one administered agent; a code indicative of at least onedetection material administered; a code indicative of the depth ofpenetration of an administered agent; or a code indicative of thecondition of at least one location of an administered frozen particlecomposition.

In at least one embodiment, the information regarding at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information regarding at least one cellular ortissue source. In at least one embodiment, the information regarding atleast one cellular or tissue source includes information regarding atleast one abnormal cellular or tissue source, and may include at leastone type of cell or tissue. In at least one embodiment of the method,the at least one frozen particle therapeutic composition includes atleast one of nitrogen, carbon dioxide, hydrogen oxide, helium, neon,xenon, krypton, air, oxygen, chlorine, bromine, argon, polyethyleneglycol, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl formamide,dioxane, hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia,acetic acid, benzene, carbon tetrachloride, acetonitrile, hexane,methylene chloride, carboxylic acid, saline, Ringer's solution, lactatedRinger's solution, Hartmann's solution, acetated Ringer's solution,phosphate buffered solution, TRIS-buffered saline solution, Hank'sbalanced salt solution, Earle's balanced salt solution, standard salinecitrate, HEPES-buffered saline, dextrose, glucose, or diethyl ether.

In at least one embodiment of the method, the at least one frozenparticle therapeutic composition includes at least one major dimensionof approximately one centimeter or less, approximately one millimeter orless, approximately one micrometer or less, approximately one nanometeror less, or any value therebetween. In at least one embodiment, the atleast one frozen particle therapeutic composition includes one or morereinforcement agents, one or more abrasives, or one or more explosiveagents.

In at least one embodiment, the method includes that the receipt by theat least one subject of at least one frozen particle therapeuticcomposition is pursuant to at least one clinical trial. In at least oneembodiment, the method further comprises determining at least onecorrelation before the onset of the at least one frozen particletherapeutic composition. In at least one embodiment, the method furthercomprises creating at least one inclusion criterion and at least oneexclusion criterion for a clinical trial involving the at least onefrozen particle therapeutic composition. In at least one embodiment, themethod further comprises suggesting the inclusion of one or more of theat least one subject in at least one clinical trial. In at least oneembodiment, the method further comprises suggesting the exclusion of oneor more of the at least one subject in at least one clinical trial. Inat least one embodiment, the method further comprises using one or moredetermination to predict at least one clinical outcome regarding atleast one second subject. In at least one embodiment, the at least onesecond subject has not received the at least one frozen particletherapeutic composition. In at least one embodiment, using one or moreof the at least one comparison includes predicting at least one clinicaloutcome involving the at least one second subject, wherein the at leastone second subject is a plurality of people; and segregating subjectidentifiers associated with the plurality of people in reference to thepredicted at least one clinical outcome. In at least one embodiment, themethod includes determining the eligibility of the at least one secondsubject for the at least one clinical trial.

In at least one aspect, a system comprises at least one computerprogram, configured with a computer-readable medium, for use with atleast one computer system and wherein the computer program includes aplurality of instructions including but not limited to one or moreinstructions for comparing information regarding at least one aspect ofat least one therapeutic administration of at least one frozen particletherapeutic composition to at least one biological tissue of at leastone subject, and information regarding at least one clinical outcomefollowing receipt by the at least one subject of at least one frozenparticle therapeutic composition.

In at least one embodiment, the information regarding at least oneaspect of therapeutic administration of at least one frozen particletherapeutic composition includes information regarding amount of the atleast one therapeutic composition or therapeutic agent administered toat least one biological tissue of at least one subject. In at least oneembodiment, the information regarding at least one aspect of therapeuticadministration of at least one frozen particle therapeutic compositionincludes information regarding at least one dimension of biologicaltissue penetration. In at least one embodiment, the informationregarding at least one dimension of biological tissue penetrationincludes information regarding at least one of depth, width, or breadthof administration of at least one frozen particle therapeuticcomposition to at least one biological tissue of at least one subject.

In at least one embodiment, the computing device is configured tocommunicate with at least one printing device, at least one imagingdevice, or at least one input device. In at least one embodiment, theinformation regarding at least one aspect of therapeutic administrationof at least one frozen particle therapeutic composition includesinformation regarding two or more subjects with one or more commonattributes. In at least one embodiment, the information regarding atleast one aspect of therapeutic administration of at least one frozenparticle therapeutic composition includes information regarding at leastone cellular or tissue source. In at least one embodiment, theinformation regarding at least one cellular or tissue source includesinformation regarding at least one abnormal cellular or tissue source.In at least one embodiment, information regarding the at least onecellular or tissue source includes information regarding at least onetype of cell or tissue.

In at least one embodiment, the system includes information relating toat least one frozen particle therapeutic composition including at leastone of nitrogen, carbon dioxide, hydrogen oxide, helium, neon, xenon,krypton, air, oxygen, chlorine, oxygen, air, bromine, argon,polyethylene glycol, acetone, ethyl acetate, dimethyl sulfoxide,dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether. In at least one embodiment, the atleast one frozen particle therapeutic composition includes at least onemajor dimension of approximately one centimeter or less, approximatelyone millimeter or less, approximately one micrometer or less,approximately one nanometer or less, or any value therebetween. In atleast one embodiment, the at least one frozen particle therapeuticcomposition includes one or more reinforcement agents, one or moreabrasives, or one or more explosive materials.

In at least one embodiment, the system includes that the receipt by theat least one subject of at least one frozen particle therapeuticcomposition is pursuant to at least one clinical trial. In at least oneembodiment, the system further comprises determining at least onecorrelation before the administration of the at least one frozenparticle therapeutic composition. In at least one embodiment, the systemfurther comprises creating at least one inclusion criterion and at leastone exclusion criterion for a clinical trial involving the at least onefrozen particle therapeutic composition. In at least one embodiment, thesystem further comprises suggesting the inclusion of one or more of theat least one subject in at least one clinical trial. In at least oneembodiment, the system further comprises suggesting the exclusion of oneor more of the at least one subject in at least one clinical trial. Inat least one embodiment, the system further comprises using one or moreof the at least one comparison to predict at least one clinical outcomeregarding at least one second subject. In at least one embodiment, theat least one second subject has not received the at least one frozenparticle therapeutic composition.

In at least one embodiment, using one or more of the at least onecomparison includes predicting at least one clinical outcome involvingthe at least one second subject, wherein the at least one second subjectis a plurality of people; and segregating subject identifiers associatedwith the plurality of people in reference to the predicted at least oneclinical outcome. In at least one embodiment, using one or more of theat least one comparison includes the at least one second subject is aplurality of people; and determining the eligibility of the at least onesecond subject for the at least one clinical trial.

In at least one aspect, a system comprises at least one computerprogram, configured with a computer-readable medium, for use with atleast one computer system and wherein the computer program includes aplurality of instructions including but not limited to one or moreinstructions for comparing information regarding at least one aspect ofat least one therapeutic administration of at least one frozen particletherapeutic composition to at least one biological tissue of at leastone subject, and information regarding at least one frozen particletherapeutic composition involving the at least one biological tissue ofthe at least one subject; and one or more instructions for applying oneor more comparisons to the information regarding the at least one aspectof therapeutic administration of at least one frozen particletherapeutic composition to a plurality of people.

In at least one embodiment, the system includes one or more instructionsfor segregating subject identifiers associated with the plurality ofpeople in reference to at least one of the one or more appliedcomparisons. In at least one embodiment, the information regarding atleast one aspect of the therapeutic administration of at least onefrozen particle therapeutic composition includes information regardingthe amount of therapeutic composition or therapeutic agent administeredto at least one biological tissue of at least one subject. In at leastone embodiment, the information regarding at least one aspect of thetherapeutic administration of at least one frozen particle therapeuticcomposition includes information regarding at least one dimension ofbiological tissue penetration. In at least one embodiment, theinformation regarding at least one dimension of biological tissuepenetration includes information relating to at least one of depth,width, or breadth of administration of the at least one frozen particletherapeutic composition to at least one biological tissue of at leastone subject. In at least one embodiment, the system includes one or moreinstructions for segregating individual identifiers associated with theplurality of people in reference to at least one characteristic sharedby two or more subjects in the plurality of people.

In at least one aspect, a computer program product includes a signalbearing medium bearing at least one of one or more instructions forreceiving a first input associated with a first possible dataset, thefirst possible dataset including data representative of one or moremeasurements relating to one or more physical attributes of a firstsubject; one or more instructions for comparing a value associated withthe first possible dataset with a second dataset including valuesrepresentative of predictive regimen parameters from a second subjectwith one or more similar or dissimilar physical attributes; one or moreinstructions for determining from the comparison at least one frozenparticle therapeutic composition regimen for the first subject; andoutput information. In at least one embodiment, the output informationis based on the comparison.

In at least one embodiment, the computer program product includes one ormore instructions for accessing the first possible dataset in responseto the first input. In at least one embodiment, the computer programproduct further comprises one or more instructions for generating thefirst possible dataset in response to the first input. In at least oneembodiment, the computer program product further comprises one or moreinstructions for determining a graphical illustration of the firstpossible dataset. In at least one embodiment, the computer programproduct further comprises one or more instructions for determining agraphical illustration of the second possible dataset. In at least oneembodiment, the computer program product includes a signal bearingmedium, such as a computer-readable medium. In at least one embodiment,the signal bearing medium includes a recordable medium, or acommunications medium.

In at least one aspect, a computer program product includes a signalbearing medium bearing at least one of one or more instructions forprocessing a first possible dataset, the first possible datasetincluding data representative of one or more measurements relating toone or more physical attributes of a first subject; one or moreinstructions for comparing a value associated with the first possibledataset with a second dataset including values representative ofpredictive regimen parameters from a second subject with one or moresimilar or dissimilar physical attributes; one or more instructions fordetermining from the comparison at least one frozen particle therapeuticcomposition treatment regimen for the first subject; and outputinformation, wherein the output information is optionally based on thecomparison.

In at least one aspect, a computer program product includes a signalbearing medium bearing at least one of one or more instructionsresponsive to a first possible dataset, the first possible datasetincluding data representative of one or more measurements relating toone or more physical attributes of a first subject; one or moreinstructions for comparing a value associated with the first possibledataset with a second dataset including values representative ofpredictive regimen parameters for a second subject with one or moresimilar or dissimilar physical attributes; one or more instructions fordetermining from the comparison at least one frozen particle therapeuticcomposition treatment regimen for the first subject; and outputinformation.

In at least one aspect, a computer program product includes a signalbearing medium bearing at least one of one or more instructions forreceiving a first input associated with a first possible dataset, thefirst possible dataset including data representative of one or moremeasurements relating to one or more physical attributes of a subject;one or more instructions for comparing a value associated with the firstpossible dataset with a second dataset including values representativeof parameters relating to one or more expected biological changesfollowing administration of one or more frozen particle therapeuticcompositions; one or more instructions for determining from thecomparison at least one biological change following administration ofone or more frozen particle therapeutic compositions to the subject; andoutput information. In at least one embodiment, the output informationis based on the comparison.

In at least one embodiment, the computer program product includes one ormore instructions for accessing the first possible dataset in responseto the first input. In at least one embodiment, the computer programproduct further comprises one or more instructions for generating thefirst possible dataset in response to the first input. In at least oneembodiment, the computer program product further comprises one or moreinstructions for determining a graphical illustration of the firstpossible dataset. In at least one embodiment, the computer programproduct further comprises one or more instructions for determining agraphical illustration of the second possible dataset. In at least oneembodiment, the computer program product includes a signal bearingmedium that includes a computer-readable medium, a recordable medium, ora communications medium.

In at least one aspect, a computer program product includes a signalbearing medium bearing at least one of one or more instructions forprocessing a first input associated with a first possible dataset, thefirst possible dataset including data representative of one or moremeasurements relating to one or more physical attributes of a subject;one or more instructions for comparing a value associated with the firstpossible dataset with a second dataset including values representativeof parameters relating to one or more expected biological changesfollowing administration of one or more frozen particle therapeuticcompositions; one or more instructions for determining from thecomparison at least one biological change following administration ofone or more frozen particle therapeutic compositions to the subject; andoutput information.

In at least one aspect, a computer program product includes a signalbearing medium bearing at least one of one or more instructionsresponsive to a first possible dataset, the first possible datasetincluding data representative of one or more measurements relating toone or more physical attributes of a subject; one or more instructionsfor comparing a value associated with the first possible dataset with asecond dataset including values representative of parameters relating toone or more expected biological changes following administration of oneor more frozen particle therapeutic compositions; one or moreinstructions for determining from the comparison at least one biologicalchange following administration of one or more frozen particletherapeutic compositions to the subject; and output information.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates particular phases of hydrogen oxide.

FIG. 2 illustrates the density of hydrogen oxide at various pressurepoints.

FIG. 3 illustrates particular phases of hydrogen oxide at variouspressure and temperature points.

FIG. 4 illustrates particular phases of hydrogen oxide at variouspressure and temperature points.

FIG. 5 illustrates the strength of hydrogen oxide samples reinforcedwith fiberglass or kaolin.

FIG. 6 illustrates the strength of hydrogen oxide samples reinforcedwith a reinforcement agent.

FIG. 7 illustrates a partial view of a method 700 that includesgenerating at least one response.

FIG. 8 illustrates a partial view and an embodiment of FIG. 7.

FIG. 9 illustrates a partial view and an embodiment of FIG. 7.

FIG. 10 illustrates a partial view of a method 1000 that includesgenerating at least one response.

FIG. 11 illustrates a partial view and an embodiment of FIG. 10.

FIG. 12 illustrates a partial view and an embodiment of FIG. 10.

FIG. 13 illustrates a partial view of a system 1300 that includes acomputer program for executing a computing process on a computingdevice.

FIG. 14 illustrates a partial view and an embodiment of FIG. 13.

FIG. 15 illustrates a partial view and an embodiment of FIG. 13.

FIG. 16 illustrates a partial view of a system 1600 that includes acomputer program for executing a computing process on a computingdevice.

FIG. 17 illustrates a partial view of a computer program product 1700for executing a computing process on a computing device.

FIG. 18 illustrates a partial view of a computer program product 1800for executing a computing process on a computing device.

FIG. 19 illustrates a partial view of a computer program product 1900for executing a computing process on a computing device.

FIG. 20 illustrates a partial view of a computer program product 2000for executing a computing process on a computing device.

FIG. 21 illustrates a partial view of a computer program product 2100for executing a computing process on a computing device.

FIG. 22 illustrates a partial view of a computer program product 2200for executing a computing process on a computing device.

FIG. 23 illustrates a partial view of a method 2300 that includesgenerating at least one response.

FIG. 24 illustrates a partial view and an embodiment of FIG. 23.

FIG. 25 illustrates a partial view and an embodiment of FIG. 23.

FIG. 26 illustrates a partial view of a method 2600 that includesgenerating at least one response.

FIG. 27 illustrates a partial view and an embodiment of FIG. 26.

FIG. 28 illustrates a partial view and an embodiment of FIG. 26.

FIG. 29 illustrates a partial view of a system 2900 that includes acomputer program for executing a computing process on a computingdevice.

FIG. 30 illustrates a partial view and an embodiment of FIG. 29.

FIG. 31 illustrates a partial view of a system 3100 that includes acomputer program for executing a computing process on a computingdevice.

FIG. 32 illustrates a partial view and an embodiment of FIG. 31.

FIG. 33 illustrates a partial view of a system 3300 that includes acomputer program for executing a computing process on a computingdevice.

FIG. 34 illustrates a partial view and an embodiment of FIG. 33.

FIG. 35 illustrates a partial view and an embodiment of FIG. 33.

FIG. 36 illustrates a partial view of a system 3600 that includes acomputer program for executing a computing process on a computingdevice.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

In at least one embodiment, at least one composition, therapeuticcomposition, device, system, product, or method disclosed herein relatesto utilizing one or more frozen particles for various purposes. In atleast one embodiment, the one or more frozen particles include at leastone frozen constituent including at least one of hydrogen oxide, helium,neon, krypton, argon, xenon, nitrogen, chlorine, bromine, oxygen, air,carbon dioxide, polyethylene glycol, acetone, ethyl acetate, dimethylsulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether. In at least one embodiment, atleast one of the constituents of the one or more frozen particles isfrozen. In at least one embodiment, all of the constituents of the oneor more frozen particles are frozen. In at least one embodiment, the atleast one composition or therapeutic composition includes one or morefrozen solution particles. In at least one embodiment, the compositionor therapeutic composition includes one or more frozen solutionparticles and the composition or therapeutic composition is in at leastone crystalline or amorphous phase. In at least one embodiment, thefrozen solution particles include at least one of the constituentsdescribed herein.

In at least one embodiment, the one or more frozen particles includefrozen hydrogen oxide particles. Frozen hydrogen oxide, or typical waterice, exists in several non-crystalline forms. Each of these forms hasspecific physical characteristics such as density and vibrationalspectra. Some of the frozen hydrogen oxide phase transformations areshown in FIG. 1. (See e.g., Chaplin, the worldwide web atIsbu.ac.uk/water; Ivanov et al., Russian J. Gen. Chem. vol. 75, pp.1851-1856 (2005), each of which is incorporated herein by reference).

Hydrogen oxide (water) has many frozen phases (ices), includingcrystalline and non-crystalline phases. The crystalline phases generallyhave the common structure of having hydrogen bonds to four neighboringwater molecules, such as two hydrogen atoms near each oxygen atom.Structural data on the known frozen hydrogen oxide polymorphs are shownin Table I, with two known phases of ice XI. (See, e.g., Chaplin, Ibid;and Zheligovskaya, et al., Russian Chem. Rev. 75, pp. 57-76, 2006, eachof which is incorporated herein by reference).

TABLE I Structural data on the ice polymorphs Dielectric Density,constant, Ice polymorph g/cm³ Protons Crystal Symmetry ε_(S) NotesHexagonal ice, Ih 0.92 disordered Hexagonal One C₆ 97.5 Cubic ice, Ic0.92 disordered Cubic four C₃ LDA, Ia 0.94 disordered Non- As prepared,crystalline may be mixtures of several types HAD 1.17 disordered Non- Asprepared, crystalline may be mixtures of several types VHDA 1.25disordered Non- crystalline II 1.17 ordered Rhombohedral One C₃ 3.66 III1.14 disordered Tetragonal One C₄ 117 protons may be partially orderedIV 1.27 disordered Rhombohedral One C₃ metastable in ice V phase space V1.23 disordered Monoclinic One C₂ 144 protons may be partially orderedVI 1.31 disordered Tetragonal One C₄ 193 protons can be partly orderedVII 1.50 disordered Cubic four C₃ 150 two interpenetrating ice Icframeworks VIII 1.46 ordered Tetragonal One C₄ 4 low temperature form ofice VII IX 1.16 ordered Tetragonal One C₄ 3.74 low temperature form ofice III, metastable in ice II space X 2.51 symmetric Cubic four C₃symmetric proton form of ice VII XI 0.92 ordered Orthorhombic three C₂low temperature form of ice Ih XI >2.51 symmetric Hexagonal distortedFound in close packed simulations only XII 1.29 disordered TetragonalOne C₄ metastable in ice V phase space XIII 1.23 ordered Monoclinic OneC₂ ordered form of ice V phase XIV 1.29 mostly Orthorhombic One C₄ordered form of ordered ice XII phase XV 1.31 ordered ? ? ordered formof (?) ice VI phase

Cooling liquid hydrogen oxide below its standard freezing pointtypically results in the formation of frozen hexagonal ice. However, ifthe hydrogen oxide is pure and cooled slowly, the liquid hydrogen oxidecan be supercooled to approximately −42° C. Amorphous solids hardenwithout crystallizing, such that if hydrogen oxide is cooled rapidly itresults in formation of a glass-like state, for example, hyperquenchedglassy water. (See e.g., Debenedetti, J. Phys. Condens. Matter, vol. 15,pp. R1669-R1726 (2003), and as cited by Chaplin, worldwideweb atIsbu.ac.uk/water; each of which is incorporated herein by reference.)Generally, hyperquenched glassy water is formed by rapidly spraying afine mist of micrometer-sized hydrogen oxide droplets into very coldliquefied gas, such as propane. Alternatively, a fine mist of hydrogenoxide can be sprayed onto a very cold frozen substrate, at or belowapproximately −193° C. Hyperquenched glassy water may also be formed bycooling capillary tubes containing bulk liquid water (˜100 μm diameter)with liquid helium at approximately −269° C.

As shown in FIGS. 1-4, hydrogen oxide attains various structures andphases depending upon the temperature or pressure of the environment. Asindicated in FIG. 1, for example, hydrogen oxide ice Ic is derived fromhigh density amorphous water or deeply supercooled liquid water, whenput under low temperature or higher pressure. Likewise, as indicated inFIG. 2, the hydrogen oxide has a greater density as a liquid than as asolid under ambient conditions (ice Ih). However, at increasingpressure, at least ice stages III, V, VI, and VII exhibit a greaterdensity than liquid hydrogen oxide. FIG. 3 indicates the phase diagramfor hydrogen oxide based on pressure and temperature variance, whileFIG. 4 shows the specific sub-categories of hydrogen oxide based onphysical properties, such as structure and density, among others, as thetemperature and pressure vary.

Similarly, amorphous solid water is formed from the slow deposition ofhydrogen oxide vapor on a cold metal crystal surface (at less thanapproximately 2 nm/s), below the temperature of approximately −153° C.Amorphous solid water is a viscous semi-solid material that has adensity of approximately 0.94 g/cm³ and harbors gaps and spaces in itsstructure, as well as reactive hydrogen bonds. These structures areremoved by annealing under vacuum pressure, which allows the material toconvert to a high density glassy water or low density amorphous ice,depending on the temperature. Typically, high density glassy water,which has a density of approximately 1.1 g/cm³, is formed by vapordeposition at approximately −263° C.

Low-density amorphous (LDA) ice also occurs from heating high-densityamorphous (HDA) ice to just above approximately −153° C. at atmosphericpressure, and transforms to cubic ice at approximately −113° C. to −123°C. Low-density amorphous ice is also prepared by submitting low-pressurephases (Ih, Ic, XI, etc.) to high pressure (approximately 1.0 GPa) atlow temperatures (e.g., below approximately −148° C.).

Very-high density amorphous (VHDA) ice is a viscous water state with adensity of approximately 1.25 g/cm³, and is prepared by heatinghigh-density amorphous ice to just above approximately −113° C. andapproximately 1.15 GPa. When very-high density amorphous ice is heatedat different pressures between 0.3 and 2 GPa, it re-crystallizes intoonly the proton disordered ices III, IV, V, XII, VI and VII in order ofincreasing pressure, but does not typically re-crystallize into theproton ordered phases (e.g., ice II).

Typically, the density of liquid water increases with increasedpressure. When liquid water approaches the critical point in theliquid-vapor phase, water enters a supercritical phase where it existsas small but liquid-like hydrogen-bonded clusters dispersed within agas-like phase and its physical properties vary according to changingdensity. Supercritical water is an excellent solvent for non-polarmolecules, due to its low dielectric constant and poor hydrogen bonding.Due to these same properties, supercritical water is typically not agood solvent for electrolytes, which tend to form ionic bonds.

As indicated in FIG. 2, hexagonal ice is less dense than liquid water,whereas the other ice phases are all denser and phase changes occur nearthe liquid and solid densities (See e.g., Loerting et al., J. Phys.:Condens. Matter vol. 18, R919-R977 (2006), which is incorporated hereinby reference). Liquid water density varies with change in temperature orpressure, whereas the density of amorphous ice varies only with changein pressure, but not temperature.

Hydrogen oxide has a high heat of vaporization (approximately 40.7kJ/mol), and a high heat of sublimation (approximately 51.059 kJ/mol at0° C.), which allows for the frozen particles to remain intact for ashort time period during which the particles are delivered to one ormore cells or tissues. These properties further enable the frozenparticles to serve as particles for delivery of at least one therapeuticcomposition to one or more cells or tissues.

Hydrogen oxide becomes more viscous as the temperature is decreased tobelow approximately 33° C., or the pressure is increased. Frozenparticles may include a “solid,” such as true solids, semi-solids, andviscous fluid, such as gels, hydrogels, or sols. Frozen particles mayinclude particles that are at least partially frozen, or are entirelyfrozen. Compositions including one or more particles may include one ormore subset groups of one or more particles, some of which may beentirely frozen and some of which may be at least partially frozen. Suchcompositions may include multiple different compositions, where thegroup of frozen particles includes at least one subset that includesmultiple particles, wherein each particle has an individual therapeuticagent or unique composition. The group of frozen particles may alsoinclude at least one subset of multiple particles, wherein each particleincludes multiple agents (including therapeutic agents).

A particular plurality of compositions or therapeutic compositions mayinclude multiple frozen particles where various multiple agents areassociated with a single particle. Likewise, a particular plurality ofcompositions or therapeutic compositions may include various multipleagents, where each individual agent is associated with a single frozenparticle. In at least one embodiment, a plurality of compositions ortherapeutic compositions may include any number of subsets of frozenparticles associated with a particular therapeutic agent or otherconstituent. During the course of any particular method describedherein, one or more plurality of compositions or therapeuticcompositions, or any particular subset thereof, may be administered in asingle treatment.

In at least one embodiment, the one or more frozen particles exist atabout 30° C., about 20° C., about 10° C., about 5° C., about 0° C.,about −10° C. about −20° C., about −30° C., about −40° C., about −50°C., about −60° C., about −70° C., about −75° C., about −80° C., about−85° C., about −90° C., about −95° C., about −100° C., about −120° C.,about −150° C., about −180° C., about −200° C., about −220° C., about−250° C., or any value less than or therebetween.

In certain instances, the one or more frozen particles are utilized at avery cold temperature so that effective penetration of a biologicaltissue is achieved. In certain instances, the one or more frozenparticles are utilized at warmer temperatures, particularly if thecontents of the one or more frozen particles include agents that havewarmer freezing temperatures. For example, the freezing point ofnitrogen is approximately −210° C., whereas the freezing point ofdimethyl sulfoxide (DMSO) is approximately 18.45° C. Thus, frozenparticles of DMSO can be utilized or administered at a warmertemperature than can frozen particles of nitrogen.

Ice Ic is generally formed by condensation of water vapor, at ambientpressure and low temperatures (less than approximately −80° C.), orbelow approximately −38° C. as a mist. (See e.g., Murray et al., Phys.Chem. Chem. Phys. Vol. 8, pp. 186-192 (2006), which is incorporatedherein by reference). Ice Ic is also prepared by reducing the pressureon high-pressure hydrogen oxide ice at approximately −196° C. It may bethe preferred phase for ice formed from hydrogen oxide droplets smallerthan about 15 nm in radius, particularly at low temperatures (e.g.,−113° C. to −53° C.). (See e.g., Johari, J. Chem. Phys. vol. 122 pp.194504 (2005); Zhang, et al., Chem. Phys. Lett. vol. 421, pp. 251-255(2006), each of which is incorporated herein by reference).

Ice Ih constitutes a large portion of naturally-occurring snow and ice.Since hexagonal ice exhibits changes in the hydrogen bonding, ice Ihshows anomalous reduction in thermal conductivity with increasingpressure (as does cubic ice and low-density amorphous ice). (See e.g.,Andersson et al., Phys. Rev. B vol. 65 pp. 140201.1-14201.4 (2002),which is incorporated herein by reference).

Ice II maintains a general rhombohedral unit shape, similar to ice I.The density of ice II is approximately 1.17 g/cm³. Ice III maintains ageneral tetragonal unit shape, with a density of approximately 1.14g/cm³. Ice VI also maintains a general tetragonal unit shape, with adensity of approximately 1.31 g/cm³. Ice VII is primarily composed ofmultiple intercalating ice Ic lattices, and has a density ofapproximately 1.66 g/cm³.

In at least one embodiment, the therapeutic composition includes atleast one of a solid, liquid, or gas. In at least one embodiment, thetherapeutic composition includes one or more of a suspension, mixture,solution, sol, clathrate, colloid, emulsion, microemulsion, aerosol,ointment, capsule, powder, tablet, suppository, cream, device, paste,liniment, lotion, ampule, elixir, spray, suspension, syrup, tincture,detection material, polymer, biopolymer, buffer, adjuvant, diluent,lubricant, disintegration agent, suspending agent, solvent, calorimetricagent, light-emitting agent, glidant, anti-adherent, anti-static agent,surfactant, plasticizer, emulsifying agent, flavor, gum, sweetener,coating, binder, filler, compression aid, encapsulation aid,preservative, granulation agent, spheronization agent, stabilizer,adhesive, pigment, sorbent, nanoparticle, or gel.

In at least one embodiment, the at least one adhesive is included in oneor more frozen particles. In at least one embodiment, the one or morefrozen particles provide a vehicle for the at least one adhesive. Incertain instances, at least one adhesive is provided to at least onebiological tissue in an inactive form, wherein the at least one adhesivepolymerizes or activates upon contact with the at least one biologicaltissue, or shortly thereafter.

In at least one embodiment, at least one scaffold (e.g., collagen,elastin, protein, carbohydrate, nucleic acid, organic chemical, or othercomponent) is provided with the at least one composition or therapeuticcomposition for one or more cells. In at least one embodiment, thescaffold provides a matrix for one or more cells. In at least oneembodiment, the one or more cells are located in at least one biologicaltissue.

In at least one embodiment, clathrate compositions are included.Clathrate ice forms from water or other liquids, and contains smallamounts of non-polar molecules (generally gases) under moderate pressureof a few MPa, and temperatures close to 0° C. Clathrate structures canvary, but generally allow a minimum amount of small molecules to fitinto and stabilize gaps without forming covalent or hydrogen bonds withthe hydrogen oxide molecules. Certain clathrates are formed at theinterface of the liquid phase, under atmospheric pressure. Clathratesinclude but are not limited to the structural forms of sI, sII, and sh.In certain instances, noble gases may be used to form clathratecompounds with hydrogen oxide or other molecules. Noble gases generallyhave low polarizability, and tend to be spherically symmetrical, whichallows for solubility with the hydrogen oxide cage. In addition, thesolubility of the noble gases increases considerably as the temperatureis lowered. The solubility of particular noble gases as clathrates withhydrogen oxide are shown in Table II. (See e.g., Dec et al., J. SolutionChem. vol. 14, pp. 417-429 (1985); Ivanov, et al., J. Struct. Chem. vol.46, pp. 253-263 (2005); Fernandez-Prini, et al., Elsvier, pp. 73-98(2004); Ivanov, et al., Russian J. Gen. Chem. vol. 75, pp. 1851-1856(2005), each of which is incorporated herein by reference.)

TABLE II Solubility properties of the noble gases Property He Ne Ar KrXe Rn Atomic number 2 10 18 36 54 86 Atomic radius, Å 1.08 1.21 1.641.78 1.96 2.11 ΔG° of solution in H₂O at 25° C., kJ/mol 29.41 29.0326.25 24.80 23.42 ΔH° of solution in H₂O at 25° C., kJ/mol −0.59 −3.80−11.98 −15.29 −18.99 ΔS° of solution in H₂O at 25° C., J/molK −100.6−110.1 −128.2 −134.5 −142.2 Solubility, mM, 5° C., 101, 325 Pa H₂O 0.410.53 2.11 4.20 8.21 18.83 D₂O 0.49 0.61 2.38 4.61 8.91 20.41 Solubilityminima, ° C. H₂O 30 50 90 108 110 D₂O 53 53 98 108 116

Other materials are included in one or more compositions describedherein. For example, liquid nitrogen is nontoxic and inert, with afreezing point at 1 atm pressure of approximately −210° C. Liquid heliumis nontoxic and inert, with a freezing point at 367 psi of approximately−272.2° C. Liquid argon is nontoxic and inert with a freezing point at 1atm pressure of approximately −189.4° C. Liquid neon has a freezingpoint of approximately −245.95° C., while liquid xenon has a freezingpoint of approximately −111.9° C. The freezing point of liquid dimethylsulfoxide (DMSO) is approximately 18.45° C., and water or otherco-solvents can decrease the freezing point. The freezing point oflactated Ringer's solution is approximately −45° C. These and othermaterials can be utilized as described herein either alone, or incombination with other materials.

In at least one embodiment, the one or more frozen particles have atleast one major dimension of approximately one decimeter or less,approximately one centimeter or less, approximately one millimeter orless, approximately one micrometer or less, approximately one nanometeror less, approximately one picometer or less, or any value therebetween.In at least one embodiment, a plurality of frozen particles is deliveredor administered, and the plurality includes at least two subsets offrozen particles which can be differentiated based on size. In at leastone embodiment, a plurality of frozen particles includes at least onesubset of frozen particles that have at least one major dimension ofapproximately ten micrometers or less. In at least one embodiment, theat least one major dimension of the one or more frozen particlesincludes at least one of radius, diameter, length, width, height, orperimeter.

In at least one embodiment, the one or more frozen particles approximatethe shape of at least one of a sphere, bullet, flechette, cone, needle,arrow, spear, diamond, pyramid, cylinder, mini ball, shuttlecock,spiral, bell, pear, crystal, cube, spheroid, tetrahedron, crescent, orhigh aspect ratio shape. The size, shape, weight, or density, as well asother physical parameters of the one or more frozen particles may beadjusted according to a particular composition or therapeuticcomposition, or desired goal in utilizing the compositions. In at leastone embodiment, the one or more frozen particles include a plurality offrozen hydrogen oxide particles that are approximately uniform withregard to size, shape, weight, or density. In at least one embodiment,the one or more frozen particles include an array of different sizes,shapes, weights, or densities.

In at least one embodiment disclosed herein, one or more reinforcementagents may be included in the compositions or therapeutic compositionsdescribed. Examples of some reinforcement agents include, but are notlimited to, polyaramid, vinylester matrix, metal, ceramic, fiberglass,cellulose, broad carbide, aromatic polyamide, nylon, silk, rayon,acetate, modacrylic, olefin, acrylic, polyester, aromatic polyester,poly-lactic acid, vinyon, saran, spandex, vinalon, aromatic nylon,vinylidene chloride, modal, polybenzimidazole, sulfur, lyocell, orlon,zylon, high-performance polyethylene, polypyridobenzimidazole, vectran,acrylonitrile rubber, glass, copper, iron, steel, sodium, potassium,calcium, zinc, manganese, carbon, magnesium, alluvium, sand, sugar,calcite, emery, diamond, novaculite, pumice, rouge, borazon, corundum,zirconia alumina, silicon, silica, frozen hydrogen oxide ice, plantmatter, animal matter, or mineral matter. In at least one embodiment,plant matter may include vegetable matter, nuts or nut products orpieces (e.g., almonds), grains (e.g., oatmeal), wood (e.g., wood fibers)or other stalk material, leaf matter, fruit matter (including pits orseeds or parts thereof), and other plant material.

In at least one embodiment, one or more reinforcement agents are made byspinning into a fiber, wire, or filament. Some non-limiting examples ofreinforcement fibers can be found at, for example, U.S. Pat. No.5,855,663; U.S. Pat. No. 5,652,058; KEVLAR® technical guide, PolymerBulletin, vol. 16, pp. 167-174 (1986), and WO/2003/060002, each of whichis incorporated herein by reference.

In at least one embodiment, the one or more reinforcement agents aremanufactured into a plate or spheroid. In certain instances, the one ormore reinforcement agents are utilized in the form of a resin, powder,solution, flake, sheet, film, ribbon, gel, ball, pellet, or bead. (Seee.g., U.S. Pat. No. 5,534,584; U.S. Pat. No. 5,331,046; each of which isincorporated herein by reference). The one or more reinforcement agentsmay be in the form of a solid, liquid, or gas.

The one or more reinforcement agents are positioned on or in the one ormore frozen particles depending on a given context. For example, thepositioning of one or more reinforcement agents may consider theparticular goal of administering the one or more frozen particles, thecomponents of the at least one composition or therapeutic composition,or the needs or desires of a particular outcome of treatment oradministration of the one or more frozen particles. In at least oneembodiment, the one or more reinforcement agents are located at least onthe surface or beneath the surface of the one or more frozen particles.In at least one embodiment, the one or more reinforcement agents arelocated within the one or more frozen particles.

As shown in FIGS. 5 and 6, the strength of hydrogen oxide ice samplesincreases when particular reinforcement agents are added. As indicatedin FIG. 5, ice samples exhibit increased strength, as measured by beamdeflection as an angle of shear when reinforced with fiberglass orkaolin. As indicated in FIG. 6, the maximum stress (in MPa) and strainrate increases when particular reinforcement agents are added to thehydrogen oxide ice samples.

In certain instances, the composition or therapeutic compositiondescribed herein includes one or more abrasives may include treated oruntreated abrasives, coated abrasives, bonded abrasives, powders,aggregates, composites, or other forms. In at least one embodiment, theone or more abrasives include, but are not limited to include, but arenot limited to, polyaramid, vinylester matrix, metal, ceramic,fiberglass, cellulose, broad carbide, aromatic polyamide, nylon, silk,rayon, acetate, modacrylic, olefin, acrylic, polyester, aromaticpolyester, poly-lactic acid, vinyon, saran, spandex, vinalon, aromaticnylon, vinylidene chloride, modal, polybenzimidazole, sulfur, lyocell,orlon, zylon, high-performance polyethylene, polypyridobenzimidazole,vectran, acrylonitrile rubber, glass, copper, iron, steel, sodium,potassium, calcium, zinc, manganese, carbon, magnesium, alluvium, sand,sugar, calcite, emery, diamond, novaculite, pumice, rouge, borazon,corundum, zirconia alumina, silicon, silica, frozen hydrogen oxide ice,plant matter, animal matter, or mineral matter. In at least oneembodiment, plant matter may include vegetable matter, nuts or nutproducts or pieces (e.g., almonds), grains (e.g., oatmeal), wood (e.g.,wood fibers) or other stalk material, leaf matter, fruit matter(including pits or seeds or parts thereof), or other plant material.

In at least one embodiment, a therapeutic composition and methods ofdelivery to at least one biological tissue include one or more frozenhydrogen oxide particles including at least one therapeutic agent;wherein the one or more hydrogen oxide particles are in one or morephases including at least one of amorphous solid water, low densityamorphous ice, high density amorphous ice, very high density amorphousice, clathrate ice, hyperquenched glassy water, ice Ic, ice II, ice III,ice IV, ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, iceXII, ice XIII, ice XIV, or ice XV.

In at least one embodiment, a therapeutic composition includes one ormore frozen solution particles and at least one therapeutic agent;wherein the therapeutic composition is in at least one crystalline oramorphous phase.

In at least one embodiment, the at least one composition or therapeuticcomposition includes at least one therapeutic agent. (See, e.g., TheMerck Index, 14^(th) Ed. Merck & Co., Inc., Whitehouse Station, N.J.(2006), which is incorporated herein by reference). Other agents thatare approved for use in humans may be utilized as at least onetherapeutic agent described herein, and may be found at the U.S. Foodand Drug Administration website on the worldwide web at fda.gov, theinformation at which is incorporated herein by reference.

In certain instances, the one or more frozen particles themselvesprovide at least one therapeutic benefit. In certain instances, the oneor more frozen particles act as vehicles for one or more therapeuticagents that provide at least one therapeutic benefit. The frozenparticles acting as vehicles for one or more therapeutic agents may beinert, or may provide additional therapeutic benefit in the overallcomposition. In at least one embodiment, at least one therapeutic agentis activated during administration of the at least one composition ortherapeutic composition to at least one biological tissue. In at leastone embodiment, at least one therapeutic agent is activated prior to orsubsequent to administration of the at least one composition ortherapeutic composition to at least one biological tissue. In at leastone embodiment, at least one therapeutic agent is activated after aprolonged time subsequent to administration of the at least onetherapeutic composition or composition to at least one biological tissue(e.g. in cases where the therapeutic agent is encased or associated witha polymer or other agent that may insulate one or more reactant orretard the explosive or decomposition process). In at least oneembodiment, the composition or therapeutic composition includes at leastone activatable therapeutic agent. In at least one embodiment, thecomposition or therapeutic composition includes at least one activatingagent or at least one inactivating agent, or both.

In certain instances, the therapeutic agent includes at least one of anorganic or inorganic small molecule, clathrate or caged compound,protocell, coacervate, microsphere, proteinoid, laminate, helical rod,liposome, macroscopic tube, niosome, sphingosome, toroid, vesiculartube, vesicle, small unilamellar vesicle, large unilamellar vesicle,large multilamellar vesicle, multivesicular vesicle, lipid layer, lipidbilayer, micelle, organelle, cell, membrane, nucleic acid, peptide,polypeptide, protein, glycopeptide, glycolipid, glycoprotein,sphingolipid, glycosphingolipid, peptidoglycan, lipid, carbohydrate,metalloprotein, proteoglycan, chromosome, nucleus, acid, base, buffer,protic solvent, aprotic solvent, nitric oxide, nitric oxide synthase,amino acid, micelle, polymer, co-polymer, or piloxymer.

In at least one embodiment, the at least one therapeutic agent includesat least one of an anti-tumor agent, antimicrobial agent, anti-viralagent, analgesic, antiseptic, anesthetic, diagnostic agent,anti-inflammatory agent, vaccine, cell growth inhibitor, cell growthpromoter, chemical debridement agent, immunogen, antigen, radioactiveagent, apoptotic promoting factor, angiogenic factor, anti-angiogenicfactor, hormone, enzymatic factor, enzyme, papain, collagenase,protease, peptidase, elastase, urea, vitamin, mineral, nutraceutical,cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,prodrug, prebiotic, blood sugar stabilizer, smooth muscle cellactivator, epinephrine, adrenaline, neurotoxin, neuro-muscular toxin,Botulinum toxin type A, microbial cell or component thereof, or virus orcomponent thereof. In at least one embodiment, the nutraceuticalincludes one or more of a flavonoid, antioxidant, beta-carotene,anthocyanin, alpha-linolenic acid, omega-3 fatty acids, yeast, bacteria,algae, other microorganisms, plant products, or animal products. In atleast one embodiment, the analgesic or anesthetic includes one or moreof any aminoamid or aminoester local anesthetic, ibuprofen, morphine,codeine, aspirin, acetaminophen, lidocaine/lignocaine, ropivacaine,mepivacaine, benzocaine, chloroprocaine, cocaine, cyclomethycaine,dimethocaine/larocaine, propoxycaine, procaine/novocaine, proparacaine,tetracaine/amethocaine, articaine, bupivacaine, carticaine,cinchocaine/dibucaine, etidocaine, levobupivacaine, piperocaine,prilocaine, trimecaine, saxitoxin, or tetrodotoxin.

In at least one embodiment, the therapeutic agent includes at least oneanti-inflammatory agent, including but not limited to steroids,non-steroidal anti-inflammatory drugs, topical anti-inflammatory agents,or subcutaneously administered non-steroidal anti-inflammatory drugs(e.g. diclofenac).

In at least one embodiment, the analgesic includes but is not limited toone or more of paracetamol (acetaminophen), non-steroidalanti-inflammatory drugs (NSAIDs), salicylates, narcotics, or tramadol.In at least one embodiment, the analgesic includes but is not limited toaspirin, rofecoxib, celecoxib, morphine, codeine, oxycodone,hydrocodone, diamorphine, pethidine, buprenorphine, amitriptyline,carbamazepine, bagapentin, pregabalin, ibuprofen, naproxen, lidocaine, apsychotropic agent, orphenadrine, cyclobenzaprine, scopolamine,atropine, gabapentin, methadone, ketobemidone, or piritramide.

In at least one embodiment, the at least one therapeutic agent includesone or more antiseptic, including but not limited to one or more of analcohol, a quaternary ammonium compound, boric acid, hydrogen peroxide,chlorhexidine gluconate, iodine, mercurochrome, octenidinedihydrochloride, phenol (carbolic acid) compounds, sodium chloride, orsodium hypochlorite.

In at least one embodiment, the antiseptic includes but is not limitedto one or more of povidone-iodine, iodine, ethanol, 1-propanol,2-propanol/isopropanol, benzalkonium chloride, cetyl trimethylammoniumbromide, cetylpyridinium chloride, benzethonium chloride, chlorhexidine,octenidine dihydrochloride, or carbolic acid.

In at least one embodiment, the antimicrobial agent includes at leastone of an anti-fungal agent, antibiotic agent, anti-bacterial,anti-parasitic agent, or anti-worm agent. In certain instances, theantimicrobial agent may occur in nature, or it may be synthetic.

In at least one embodiment, the at least one therapeutic agent includesone or more anti-tumor agent, at least one of which may also beidentified as a cytotoxic agent, or chemotherapy agent. Non-limitingexamples of an anti-tumor agent for use as described herein include atleast one of an alkylating agent, antimetabolite, anthracycline, plantalkaloid (such as paclitaxel), topoisomerase inhibitor, monoclonalantibody, or tyrosine kinase inhibitor. In at least one embodiment, thetherapeutic agent includes one or more of imatinib, mechlorethamine,cyclophosphamide, chlorambucil, azathioprine, mercaptopurine, vincaalkaloid, taxane, vincristine, vinblastine, vinorelbine, vindesine,podophyllotoxin, etoposide, teniposide, amsacrine, dactinomycin,trastuzumab, cetuximab, rituximab, bevacizumab, dexamethasone,finasteride, tamoxifen, goserelin, telomerase inhibitor,dichloroacetate, aminopterin, methotrexate, pemetrexed, raltitrexed,cladribine, clofarabine, fludarabine, pentostatin, thioguanine,cytarabine, decitabine, fluorouracil/capecitabine, floxuridine,gemcitabine, enocitabine, sapacitabine, chloromethine, cyclophosphamide,ifosfamide, melphalan, bendamustine, trofosfamide, uramustine,carmustine, fotemustine, lomustine, nimustine, prednimustine,ranimustine, semustine, spretpozocin, carboplatin, cisplatin,nedaplatin, oxaliplatin, triplatin tetranitrate, satraplatin, busulfan,mannosulfan, treosulfan, procarbazine, decarbazine, temozolomide,carboquone, ThioTEPA, triaziquone, triethylenemelamine, docetaxel,larotaxel, ortataxel, tesetaxel, vinflunine, ixabepilone, aclarubicin,daunorubicin, doxorubicin, epirubicin, idarubicin, amrubicin,pirarubicin, valrubicin, zorubicin, metoxantrone, pixantrone,actinomycin, bleomycin, mitomycin, plicamycin, hydroxyurea,camptothecin, topotecan, irinotecan, rubitecan, belotecan, altretamine,amsacrine, bexarotene, estramustine, irofulven, trabectedin, cetuximab,panitumumab, trastuzumab, rituximab, tositumomab, alemtuzumab,bevacizumab, edrecolomab, gemtuzumab, axitinib, bosutinib, cediranib,dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib,nilotinib, semaxanib, sorafenib, sunitinib, vandetanib, alvocidib,seliciclib, aflibercept, denileukin diftitox, aminolevulnic acid,efaproxiral, porfimer sodium, talaporfin, temoporfin, verteporfin,alitretinoin, tretinoin, anagrelide, arsenic trioxide,asparaginase/pegaspergase, atrasentan, bortezomib, carmofur, celecoxib,demecolcine, elesclomol, elasamitrucin, etoglucid, lonidamine,lucanthone, masoprocol, mitobronitol, mitoguanzone, mitotane,oblimersen, omacetaxine, sitimagene ceradenovec, tegafur, testolactone,tiazofurine, tipifamib, or vorinostat.

In at least one embodiment, at least one nutraceutical is included. Atleast one nutraceutical includes but is not limited to one or more of anextract of plant or animal matter (e.g., an oil, aqueous, or solidextract), a vitamin, a mineral, a mixture or solution, a foodsupplement, a food additive, a food fortification element, or othernutraceutical. In at least one embodiment, at least one nutraceuticalincludes but is. not limited to resveratrol, an antioxidant, psyllium,sulforaphane, isoflavonoid, alpha-linolenic acid, beta-carotene,anthocyanins, phytoestrogens, polyphenols, polyphenons, catechins,benzenediols, tannins, phenylpropanoids, caffeine, alcohol, or others.

In at least one embodiment, at least one therapeutic agent includes oneor more vaccine. In at least one embodiment, the therapeutic compositionincluding at least one vaccine includes at least one prophylacticvaccine or therapeutic vaccine. In at least one embodiment, the at leastone therapeutic vaccine includes at least one anti-cancer vaccine. In atleast one embodiment, the at least one vaccine includes at least one ofan anti-tumor agent, antimicrobial agent, anti-viral agent, immunogen,antigen, live microbe, dead microbe, attenuated microbe, microbe orcomponent thereof, live virus, recombinant virus, killed virus,attenuated virus, virus component, plasmid DNA, nucleic acid, aminoacid, peptide, protein, glycopeptide, proteoglycan, glycoprotein,glycolipid, sphingolipid, glycosphingolipid, cancer cell or componentthereof, organic or inorganic small molecule, or toxoid.

One or more vaccine may include but not be limited to vaccinescontaining killed microorganisms (such as vaccines for flu, cholera,bubonic plague, and hepatitis A), vaccines containing live, attenuatedvirus or other microorganisms (such as vaccines for yellow fever,measles, rubella, and mumps), live vaccine (such as vaccines fortuberculosis), toxoid (such as vaccines for tetanus, diphtheria, andcrotalis atrox), subunit of inactivated or attenuated microorganisms(such as vaccines for HBV, VLP, and HPV), conjugate vaccines (such asvaccines for H. influenzae type B), recombinant vector, DNA vaccination.In at least one embodiment, the at least one vaccine includes but is notlimited to rubella, polio, measles, mumps, chickenpox, typhoid,shingles, hepatitis A, hepatitis B, diphtheria, pertussis, rotavirus,influenza, meningococcal disease, pneumonia, tetanus, rattlesnake venom,virus-like particle, or human papillomavirus, or anti-cancer vaccine.

In at least one embodiment, the at least one therapeutic agent includesat least one adjuvant. The at least one adjuvant may include but not belimited to one or more organic or inorganic compounds. The at least oneadjuvant may include but not be limited to at least one of a liposome,virosome, lipid, phospholipid, mineral salt, single-stranded DNA,double-stranded RNA, lipopolysaccharide, molecular antigen cage, CpGmotif, microbial cell wall or component thereof, squalene, oil emulsion,surfactant, saponin, isolated microbial toxin, modified microbial toxin,endogenous immunomodulator, or cytokine.

In one non-limiting example, a therapeutic composition includes one ormore frozen particles including paclitaxel and at least one otherconstituent including at least one of air, oxygen, nitrogen, carbondioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,bromine, or argon.

In one non-limiting embodiment, a therapeutic composition includes oneor more frozen particles including one or more pegylated cytokines orone or more anti-tumor compounds; wherein the one or more frozenparticles include nitrogen, air, oxygen, carbon dioxide, hydrogen oxide,helium, xenon, krypton, chlorine, bromine, or argon.

In at least one embodiment, the one or more frozen particles provide avehicle for delivery of the therapeutic agent. In at least oneembodiment, the at least one therapeutic agent is located in at leastone distinct region of the one or more frozen particles. In at least oneembodiment, the that least one therapeutic agent is located in aphysically or chemically separable compartment from at least one otherregion of the one or more frozen particles. In at least one embodiment,the at least one therapeutic agent is located on the surface or beneaththe surface of the one or more frozen particles. In at least oneembodiment, the at least one therapeutic agent is physically orchemically segregated from at least one other portion of the therapeuticcomposition. In at least one embodiment, the at least one distinctregion of the particle is segregated by at least one of an impermeable,permeable, or semi-permeable partition. In certain instances, thetherapeutic agent separates from the rest of the frozen particle uponadministration of the therapeutic agent to a biological tissue.

As described herein, at least one embodiment includes administering atleast one of a polymer, biopolymer, nanoparticle, or detection materialin addition to a composition or therapeutic composition (including atleast one vaccine). Such polymer, biopolymer, nanoparticle, or detectionmaterial may allow for visualization of the administration process, orprovide other benefits (including therapeutic benefits).

In certain instances, the detection material may be located on or in theone or more frozen particles, or it may be intermixed with the one ormore frozen particles. In certain instances, the detection materialprovides a “tracer” agent that allows for visualization of one or morelocations of administration of the at least one therapeutic composition,or the at least one frozen particle. Thus, in certain instances thedetection material is located on the at least one therapeuticcomposition or the at least one frozen particle. In other instances, thedetection material is separate from the at least one therapeuticcomposition or the at least one frozen particle and forms a mixture withthe therapeutic composition or frozen particles or is administered atapproximately the same time, in approximately the same place, or inapproximately the same manner as the one or more therapeuticcompositions or frozen particles.

In at least one embodiment, detection material includes a detectablelabel including but not limited to, a colorimetric label, a radioactivelabel, a light-emitting label (such as a luminescent compound, afluorescent compound, a phosphorescent compound, or a quantum dot), anucleic acid label, a protein label, an antibody label, a ligand label,a receptor label, a magnetic label, or other detectable label. In atleast one embodiment, the at least one detection material includes butis not limited to at least one electronic identification device. In atleast one embodiment, the at least one electronic identification deviceincludes at least one radio frequency identification device.

In at least one embodiment, the at least one detection material includesbut is not limited to, at least one radioactive element. In at least oneembodiment, the radioactive element includes but is not limited to ³²P,³⁵S, ¹³C, ¹³¹I, ¹⁹¹Ir, ¹⁹²Ir, ¹⁹³Ir, ²⁰¹Tl, or ³H. In at least oneembodiment, the at least one detection material includes at least onecolorimetric substance. In at least one embodiment, the at least onecolorimetric substance includes one or more of an inorganic, organic,biological, natural, artificial, or synthetic substance. Thecolorimetric substance may include, but not be limited to a dye,pigment, or a light-emitting substance, such as a luminescent substance,a fluorescent substance, phosphorescent substance, or quantum dot. In atleast one embodiment, the at least one colorimetric substance isbiocompatible.

Some examples of colorimetric substances include, but are not limitedto, colored agents that have an affinity to a substrate, such as aciddyes (e.g., water-soluble anionic dyes), basic dyes (e.g., water-solublecationic dyes), direct or substantive dyes (e.g., stains for nucleicacids, proteins, lipids, carbohydrates, cell populations, tissues, ororganelles), mordant dyes, vat dyes, reactive dyes, disperse dyes, azodyes, sulfur dyes, food dyes, solvent dyes, carbene dyes, or others.Some examples of chromophores that may be utilized include, but are notlimited to, dyes that are based on or derivatives of acridine,anthraquinone, arymethane (e.g., diphenyl methane, triphenyl methane),—N═N azo structure, phthalocyanine, diazonium salts, —NO₂ nitrofunctional group, —N═O nitroso functaional group, phthalocyanine,quinine, azin, eurhodin, safranin, indamin, indophenol, oxazin, oxazone,thiazin, thiazole, xanthene, fluorine, pyronin, fluorine, rhodamine, orothers. In at least one embodiment, the colorimetric substance includestrypan blue.

In at least one embodiment, the colorimetric substance includes one ormore fluorescent tags, including but not limited to fluorescein,phycobilin, phycoerythrin, phycourobilin, chlorophyll, phycocyanin,allophycocyanin, green fluorescent protein, or others. In at least oneembodiment, the colorimeteric substance includes at least onelight-emitting substance, including but not limited to luminescentsubstances (e.g. bioluminescent substances, chemiluminescent substances,luciferin, isoluminol, luminescent minerals, etc.).

In at least one embodiment, the at least one detection material includesbut is not limited to at least one of a diamagnetic particle,ferromagnetic particle, paramagnetic particle, super paramagneticcontrast agent, or other magnetic particle.

In at least one embodiment, a method or composition described hereinincludes one or more explosive materials. Explosive materials aretypically chemically or energetically unstable or produce a suddenexpansion of the material with a change in pressure. Such a suddenexpansion of the material under pressure changes is generallyaccompanied by the production of heat. Explosive materials are generallydifferentiated according to their decomposition rates. Generally, achemical decomposition rate of an explosive material takes years, days,hours, minutes, seconds, or a fraction of a second. Certain explosivematerials are relatively stable, and may maintain their explosiveability for some amount of time. Other explosive materials haverelatively high rates of decomposition and detonate rapidly.

Explosive materials may contain at least one oxidizer that provides fuelfor certain explosive materials. In certain instances, the oxidizer maybe an oxidizing element, such as oxygen. In certain instances, theoxidizer reacts with a reactive metal; an example of such a compoundincludes reacting fine metal powder (e.g., aluminum or magnesium) withan oxidizer (e.g., potassium chlorate or perchlorate). Chemically purecompounds may have high decomposition rates and lead to an explosion,including but not limited to nitroglycerin, acetone peroxide,trinitrotoluene, nitrocellulose, carbon, carbon monoxide, chlorine,potassium nitrate, sulfur, nitrogen compounds (such as nitrite, nitrate,and azide), potassium chlorate and potassium nitrate, hydrogen, ammoniumnitrate, phosphorous, dinitrogen tetroxide, or others. In at least oneembodiment, one or more mixtures of organic materials and oxidizers areincluded. In at least one embodiment, one or more mixtures of reactivemetals and oxidizers or oils are included.

In at least one embodiment, the one or more explosive materials includecarbon dioxide gas. Carbon dioxide gas can be entrapped into variouscompositions or therapeutic compositions described herein. One method ofincorporating carbon dioxide gas into at least one composition ortherapeutic composition includes liquefying the composition ortherapeutic composition and introducing carbon dioxide gas whilemaintaining the mixture under pressure. (See e.g., U.S. Pat. Nos.4,289,794; 4,289,790; 4,262,029; 5,439,698, each of which isincorporated herein by reference).

In at least one embodiment, the one or more explosive materials includesodium bicarbonate. In at least one embodiment, the one or moreexplosive materials include citric acid. In at least one embodiment, theone or more explosive materials include sodium bicarbonate and citricacid. In at least one embodiment, the one or more explosive materialsinclude hydrogen peroxide.

In certain instances, the at least one composition or therapeuticcomposition explodes during administration of the composition ortherapeutic composition. In certain instances, the at least onecomposition or therapeutic composition explodes prior to or subsequentto administration of the composition or therapeutic composition to atleast one biological tissue. In certain instances, the at least onecomposition or therapeutic composition explodes after a prolonged timesubsequent to administration or delivery to at least one biologicaltissue (e.g. in cases where the explosive material is encased orassociated with a polymer or other agent that may insulate one or morereactant or retard the explosive or decomposition process).

In at least one embodiment, at least one gasified frozen particle isformed by contacting fluid with gas under high pressure for a sufficienttime period to form a gas hydrate. This gas hydrate is then cooled to alower temperature in order to freeze the remaining unreacted fluid andentrap the gas hydrate. As one non-limiting example, aqueous liquid andcarbon dioxide were kept in contact at approximately 0° C. for a timesufficient under a pressure range including at least approximately 200psig to approximately 600 psig, while permitting absorption in theliquid of the gas in bound form and formation of the gasified ice. Thisprocess yields approximately 25-27.5 milliliters of gas per gram of ice.(See e.g., U.S. Pat. Nos. 4,487,023; 2,975,603; 3,086,370; 3,217,503,and 4,404,807, each of which is incorporated herein by reference).

Similarly, as described in U.S. Pat. No. 2,975,603, which isincorporated herein by reference, water contacted with carbon dioxide ata pressure of approximately 400 psig, in a temperature bath ofapproximately 0° C., is subsequently placed at −10° C. for 24 hours toeffect degasification. As described in U.S. Pat. No. 2,975,603, theresulting product yields approximately 75 volumes of carbon dioxide pergram of ice. Additionally, as described in U.S. Pat. No. 3,086,370,which is incorporated herein by reference, gasified ice products areproduced in a similar manner that contain other gases, such as nitrousoxide, sulfur-containing gases, chlorine-containing gases, inert gases,or carbon monoxide.

In at least one embodiment, compositions described herein include one ormore explosive materials that may include, for example, at least one ofa high explosive or a low explosive. In at least one embodiment, the oneor more explosive materials include at least one of carbon dioxide,nitroglycerine, or a reactive metal. In certain instances, one or morecompositions disclosed herein, including therapeutic compositions,maintain one or more explosive properties. In certain instances, the oneor more explosive properties are the result of activation of one or moreexplosive materials. In certain instances, the one or more explosiveproperties are the result of inherent tendencies of the compositionsthemselves. In certain instances, the one or more explosive propertiesrelate to an external event or stimulus, such as a change in temperatureor pressure. In certain instances, the one or more explosive propertiesrelate to a change in light intensity. In certain instances, the one ormore explosive properties relate to a change in the composition uponadministration or contact with at least one composition, cell, tissue,or subject. In certain instances, the one or more explosive propertiesresult from a temperature or pressure increase relating to penetrationof at least one cell, tissue, or subject. In certain instances, the oneor more explosive properties result from contact with water or othermoisture in a cell or tissue. In addition to the intensity of the one ormore explosives, the one or more explosive materials may differ withregard to the volatility, density, toxicity, hygroscopicity, or brisanceof a particular explosive material.

In at least one embodiment, at least one pharmaceutically-acceptablecarrier or excipient is included in a therapeutic composition. The atleast one pharmaceutically-acceptable carrier or excipient may take theform of a solid, liquid, gas, or any combination thereof. In certaininstances, the at least one pharmaceutically-acceptable carrier orexcipient includes one or more of air, oxygen, nitrogen, carbon dioxide,hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine, orargon. In at least one embodiment, the at least onepharmaceutically-acceptable carrier or excipient includes but is notlimited to polyethylene glycol, acetone, ethyl acetate, dimethylsulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether. In at least one embodiment, the atleast one pharmaceutically-acceptable carrier or excipient functions asa vehicle, or means to transport another agent. In at least oneembodiment, the at least one pharmaceutically-acceptable carrier orexcipient provides at least one clinical benefit.

As described herein, at least one composition or therapeutic compositiondescribed herein is useful in one or more methods, including one or moreof a method for abrasion of at least one biological tissue surface of asubject by delivering at least one composition to at least one surfaceof at least one biological tissue of a subject in a manner sufficient toabrade the at least one surface of the at least one biological tissue; amethod of delivering at least one therapeutic agent to at least onebiological tissue; a method of vaccinating a subject; a method oftreating a tissue related to transplantation; a method for cleaning oneor more wounds; a method for debridement of tissue or cells; a methodfor removing material from one or more blood vessel, and others. Theseand other methods include utilizing one or more composition ortherapeutic composition described hererein.

In at least one embodiment, a method for abrasion of at least onebiological tissue surface of a subject includes delivering at least onecomposition to at least one surface of at least one biological tissue ofa subject in a manner sufficient to abrade the at least one surface ofthe at least one biological tissue.

As indicated herein, in at least one embodiment, a method for providingat least one therapeutic agent to at least one biological tissue of asubject is included. In at least one embodiment, the at least onetherapeutic agent is delivered to at least one biological tissue priorto, during, or subsequent to surgery. In certain instances, at least onetherapeutic agent includes one or more therapeutic agents describedherein. In at least one embodiment, a method of providing at least onetherapeutic agent to at least one biological tissue of a subjectincludes delivering at least one therapeutic composition to at least onebiological tissue, including one or more frozen hydrogen oxide particlesincluding at least one therapeutic agent; wherein the at least onetherapeutic composition has at least one crystalline or amorphous phase.

In certain aspects, a method relates to vaccinating a subject byadministering at least one therapeutic composition that includes atleast one vaccine. The therapeutic composition can be administeredsingularly, or in conjunction with another treatment, such as surfaceabrasion therapy. In at least one embodiment, a method of vaccinating asubject includes administering to a subject at least one therapeuticcomposition; wherein the at least one therapeutic composition includesone or more frozen hydrogen oxide particles, and at least one vaccine;wherein the therapeutic composition has at least one crystalline oramorphous phase.

In at least one embodiment, a method of vaccinating a subject includesadministering to a subject at least one therapeutic composition; whereinthe at least one therapeutic composition includes one or more frozenparticles, including at least one of polyethylene glycol, acetone, ethylacetate, dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether; and at leastone vaccine.

As disclosed herein for other embodiments, a method of vaccinating asubject includes administering at least one therapeutic composition thatincludes one or more abrasives, one or more reinforcement agents, or oneor more explosive materials. In at least one embodiment, the vaccinedescribed herein relates to a therapeutic or prophylactic vaccine, andin certain instances the vaccine relates to an anti-cancer vaccine. Inat least one embodiment, the one or more abrasives are the same as theone or more reinforcement agents, or the one or more explosivematerials. In at least one embodiment, the one or more abrasives aredifferent than the one or more reinforcement agents. In at least oneembodiment, the one or more abrasives are different than the one or moreexplosive materials. In at least one embodiment, the subject receivingthe vaccine includes one or more of a vertebrate or invertebrate, insectcells, insects, bacteria, algae, plankton, or protozoa. In at least oneembodiment, the at least one subject includes one or more of a reptile,mammal, amphibian, bird, or fish. In at least one embodiment, the atleast one subject includes at least one human. In at least oneembodiment, the at least one subject includes at least one of livestock,pet, undomesticated herd animal, wild animal, or product animal. Incertain instances, the vaccine compositions and methods relate tovaccinating wildlife animals (e.g. vaccinating raccoons for rabies, orbison for brucellosis). In certain instances, the vaccine compositionsand methods described herein relate to vaccinating domesticated animals(such as cattle, horses, sheep, or goats). In certain instances, vaccinecompositions and methods described herein relate to vaccinating a groupof subjects, such as a population, a herd, a pride, a gaggle, a pack,flock, band, cluster, school, brood, troop, colony, or other group. Incertain instances, vaccinating a group of subjects is included as aroute to regulate or control infection within a group of subjects.

In at least one embodiment, the at least one subject includes at leastone of a sheep, goat, frog, dog, cat, rat, mouse, vermin, monkey, duck,horse, cow, pig, chicken, shellfish, fish, turkey, llama, alpaca, bison,wolf, fox, coyote, deer, rabbit, guinea pig, yak, chinchilla, mink,reindeer, elk, deer, raccoon, camel, donkey, or mule.

As discussed herein, particular methods are disclosed for abrading orablating at least one surface of at least one biological tissue.Abrading at least one surface of at least one biological tissue mayentail debridement of at least one biological tissue. In certaininstances, debridement may include removal or destruction of dead,damaged, or infected cells or tissues. In certain instances, debridementmay be included as part of an additional course of treatment (e.g.,surgery). In at least one embodiment, debridement may includepenetrating one or more healthy cells or tissues in order to facilitatehealing. In at least one embodiment, debridement may include penetratingone or more healthy cells or tissues near in proximity to one or moreunhealthy cells or tissues of a subject.

In at least one embodiment, one or more of the debridement methodsdescribed herein include penetrating one or more cells or biologicaltissues of a subject with at least one composition or therapeuticcomposition, wherein the one or more cells or tissues are chemically orphysically partitioned or segregated from at least one other part of thetissue or another tissue. In at least one embodiment, a method fordebridement of at least one biological tissue of a subject includesdelivering at least one composition or therapeutic composition to atleast one biological tissue of a subject wherein the at least onebiological tissue is partitioned from another biological tissue or partof another biological tissue, and at least one composition ortherapeutic composition penetrates the at last one biological tissuewith or without removing any tissue. In certain instances, a therapeuticagent is included with the at least one composition or therapeuticcomposition, as described herein. In certain instances, one or morereinforcement agents or one or more explosive materials may be includedin the at least one composition or therapeutic composition.

In at least one embodiment, the one or more frozen particles aredelivered or administered to the at least one biological tissue in adirected manner such that the tissue is etched, tattooed, shaped,carved, or otherwise modified in a directed outcome. In at least oneembodiment, the directed manner is predetermined based on information,such as from the at least one biological tissue, the subject, the atleast one composition or therapeutic composition, the context of thedebridement, the health of the subject, or other information.

In at least one embodiment, the at least one biological tissue includesone or more of skin, scalp, hair, nail, nail bed, teeth, eye, ear,ovary, oviduct, tongue, tonsil, adenoid, liver, bone, pancreas, stomach,blood vessel, blood, lymph, heart, lung, brain, breast, kidney, bladder,urethra, ureter, gall bladder, uterus, prostate, testes, vas deferens,fallopian tubes, large intestine, small intestine, esophagus, oralcavity, nasal cavity, otic cavity, connective tissue, muscle tissue, oradipose tissue. Other cells or tissues of a subject are describedherein.

In at least one embodiment, a method for removing one or more materialsfrom at least one biological tissue includes delivering at least onecomposition or therapeutic composition to the at least one biologicaltissue. In at least one embodiment, the at least one biological tissueincludes one or more tissues described herein. In at least oneembodiment, the one or more materials may include one or more materialsdescribed herein.

In at least one embodiment, a method for removing one or more materialsfrom at least one blood vessel of at least one subject includesdelivering at least one composition to at least one blood vessel of asubject in a manner sufficient to remove one or more materials.

In certain instances, a method for abrasion of at least one biologicaltissue or organ surface related to transplantation is included. In atleast one embodiment, the at least one biological tissue or organincludes one or more of the biological tissues or organs describedherein.

In at least one embodiment, a method for abrasion of at least onebiological tissue or organ surface related to transplantation includesone or more of biological tissues or organs described herein.

In at least one embodiment, a method for cleaning one or more wounds isincluded. In at least one embodiment, the one or more wounds are locatedin at least one biological tissue or organ described herein, includingbut not limited to skin tissue, muscle tissue, eye tissue, an organ,connective tissue, neoplastic tissue, or bone tissue. In at least oneembodiment, the one or more wounds are located in at least one subjectdescribed herein. In at least one embodiment, at least one therapeuticagent is included in at least one composition for cleaning one or morewounds. The one or more wounds include but are not limited to at leastone of an incision, laceration, abrasion, puncture wound, penetrationwound, gunshot wound, iatrogenic wound, severing, infection, ulcer,pressure sore, lesion, chemical burn (including but not limited toexposure to an irritant, plant, or synthetic chemical), dental caries,first-degree burn, second-degree burn, third-degree burn, fourth-degreeburn, fifth-degree burn, or sixth-degree burn. In certain instances, thewound may be a result of a bite, such as a bite from an animal, insect,or arachnid.

In at least one embodiment, a plurality of frozen particles isadministered for a particular treatment. In some instances, theplurality of frozen particles includes multiple different compositionsor therapeutic compositions. In some instances, the plurality of frozenparticles includes one or more subsets of one or more frozen particleswith common characteristics. In some instances, one or more subsets ofthe plurality of frozen particles may include but not be limited to oneor more frozen particles that have approximately the same size, shape,weight, or density; one or more subsets of the plurality of frozenparticles may include but not be limited to one or more frozen particlesthat include similar therapeutic agents; one or more subsets may includebut not be limited to one or more frozen particles that are delivered atapproximately the same time, with approximately the same velocity, or toapproximately the same location.

In certain instances, it is desirable to deliver the one or more frozenparticles to at least one cell or tissue, or administer the one or morefrozen particles to at least one subject. In at least one instance, theone or more frozen particles include a plurality of frozen particlesthat include two or more subsets of frozen particles that are deliveredor administered in sequential order. In at least one embodiment, thesequential order is predetermined, based on factors relating to, forexample, the at least one cell or tissue, the at least one subject, orthe at least one composition or therapeutic composition. In at least oneembodiment, the sequential order is determined during the course ofdelivery or administration of at least one of the one or more frozenparticles or at least one composition or therapeutic composition. In atleast one embodiment, the sequential order is determined by a softwareprogram. In at least one embodiment, the sequential order of delivery israndomized.

In at least one embodiment, the sequential order includes one or moresubsets of frozen particles that vary in size, shape, weight, density,location of delivery or administration, time of delivery oradministration, or velocity of delivery or administration. In at leastone embodiment, one or more subsets of frozen particles are delivered oradministered according to a course of treatment (e.g., at least onesubset of relatively small frozen particles are administered first,followed by at least one subset of relatively larger frozen particles;at least one subset of frozen particles are administered in a relativelyfast velocity, followed by at least one subset of frozen particlesadministered by a relatively slow velocity; at least one subset offrozen particles approximately shaped as spheroids are administeredfollowed by at least one subset of frozen particles approximately shapedas bullets, etc.).

In at least one embodiment, one or more methods described herein includedelivering or administering one or more frozen particles by highvelocity impact. In at least one embodiment, the one or more devicesthat utilize high velocity impact delivery provide at least one oflocalized delivery, targeted delivery, sustained delivery, modulateddelivery, feedback controlled delivery. In some instances, an example ofa device that may be used for administering one or more of thecompositions described herein includes a handheld device, such as awand, a pen, a baton, a hose, a sprayer, a gun (e.g., a pellet gun), orother handheld device. In certain instances, the device is at least partof a built-in delivery device, such as may be included in a wall, anoverhead device, a corral, a gate, or a device that includes a cavityinto which a subject may be placed for administration or delivery of atleast one composition described herein. In certain instances, the devicehas robotic action: In any of these instances, the device may beremotely controlled, for example, by a human or computer program.

In at least one embodiment, delivering the at least one composition,including at least one therapeutic composition, to at least onebiological tissue includes at least one of accelerating, ejecting, orpropelling, the composition or therapeutic composition toward the atleast one biological tissue. In at least one embodiment, the at leastone composition is accelerated, ejected, or propelled to or at apredetermined pressure or velocity for delivery of the at least onecomposition to a desired location on or in the at least one biologicaltissue. In certain instances, the at least one composition ortherapeutic composition is accelerated, ejected, or propelled at aparticular pressure or velocity. In certain instances, the at least onecomposition or therapeutic composition is accelerated, ejected, orpropelled at a predetermined pressure or velocity.

The velocity or pressure determined for delivery of the at least onecomposition to at least one biological tissue depends on certainfactors, including but not limited to, size and density of the particle,content of the particle, desired effect or outcome of administration ofthe particle, density of the target tissue, density of surroundingtissue, type of tissue, architecture of the tissue, and other factors.In certain instances, the desired velocity or pressure for accelerating,ejecting, or propelling the at least one composition described hereinwill be the minimum velocity or pressure needed to achieve desiredpenetration of the tissue with the composition, whether for surfaceabrasion, therapeutic delivery, or other goal.

The means for accelerating, ejecting, or propelling the compositionsdescribed herein are non-limiting, and may include general methods formaking, formulating, and delivering to at least one biological tissue bycarrier gas under pressure, mechanical or electrical impulse assistance,centripetal or centrifugal force, or others, some of which are describedherein. (See e.g., U.S. Pat. No. 4,945,050 and PCT application WO92/01802, each of which is incorporated herein by reference). In certaininstances, the one or more frozen particles are made, propelled,accelerated, or ejected simultaneously. Thus, the frozen particles maybe made while propelled, the frozen particles may be made whileaccelerated, the frozen particles may be made while ejected, or anycombination thereof.

In at least one embodiment, the one or more frozen particles aredelivered or administered by a piezoelectric-type apparatus or device,by ultrasound-mediated transdermal drug transport, or by other device.When a voltage is applied, a piezoelectric-type apparatus generates apressure pulse by change in shape or size of a chamber containing afluid (or solid), and the pressure pulse drives the contents from thechamber. In one particular instance, a high velocity device (such as apowderject, air guns, or slingshot type devices) is utilized forinjection of particles formulated with at least one therapeutic agent,for example, for therapy or prevention of a disease or condition.

For example, a powderject system, as described by Kumar and Philip(Trop. J. Pharm. Res., vol. 6, No. 1, pp. 633-644 (2007), which isincorporated herein by reference) propels frozen drug particles into theskin by means of high-speed gas flow (such as helium) that is usuallypainless and causes minimal bleeding or damage to the skin. (See alsoe.g., Tang et al., Pharm. Res., vol. 19, pp. 1160-69 (2002), which isincorporated herein by reference). As described by Kumar and Philip,particles contained in a cassette between two polycarbonate membraneslocated at the end of a chamber (Trop. J. Pharm. Res., vol. 6, No. 1,pp. 633-644 (2007), which is incorporated herein by reference). Asdescribed by Kumar and Philip, the polycarbonate membranes are rupturedwhen a carrier gas enters the chamber under high pressure, and the rapidexpansion of the gas forms a shock wave that travels down the nozzle ata speed of approximately 600-900 m/s. Kumar and Philip report drugparticle velocities of up to about 800 m/s at the nozzle exit, and themomentum density of the particles within the gas flow can be optimizedfor desired depth of penetration upon delivery to a biological tissue.(Trop. J. Pharm. Res., vol. 6, No. 1, pp. 633-644 (2007), which isincorporated herein by reference). In the powderject system, particlevelocity is controlled by nozzle geometry, membrane burst strength, andgas pressure. (See e.g., U.S. Pat. Nos. 5,630,796; and 5,699,880, whichare incorporated herein by reference).

Metered-dose transdermal sprays may also be used for delivery of atleast one therapeutic composition as described herein. As described byRathbone, et al., in one particular example, a topical solutioncontaining a volatile then nonvolatile vehicle including a therapeuticagent is administered as a single-phase solution. (See Rathbone, et al.,Modified Release of Drug Delivery Technology, NY, Marcel Dekker, Inc.vol. 126, pp. 471-619 (2004), which is incorporated herein byreference). A finite metered-dose application of the formulation tointact skin results in evaporation of the volatile component, leavingthe remaining nonvolatile penetration enhancer or therapeutic agent topartition into the stratum corneum and creating a reservoir of thetherapeutic agent(s). (See Rathbone, Ibid; and Kumar, et al., Trop. J.Pharm. Res., vol. 6, pp. 633-644 (2007), each of which is incorporatedherein by reference).

In addition to these particular examples of devices that can be utilizedfor administration of the therapeutic compositions described herein, thetherapeutic compositions can be administered in conjunction with otherdelivery devices or avenues. Likewise, the compositions described hereinfor abrasion of at least one biological tissue can be delivered to theat least one tissue by any means described herein. Some such means fordelivery of the compositions described herein include, but are notlimited to, ultrasound, iontophoresis (which involves applying anelectrical potential across skin or other tissue in order to increasepenetration of ionizable drugs), diffusion, electroporation,photomechanical waves (such as by producing pulses with Q-switched ormode-locked lasers to the skin or other tissue), needle-free injections,electro-osmosis, artificial vesicles, laser radiation, magnetophoresis(utilizing a diamagnetic substance for use with a magnetic field forincreased penetration of the composition into the biological tissue),microscissuining, controlled heat aided delivery (which involves heatingthe skin prior to or during therapeutic administration), or tattoos andetchings.

Some non-limiting examples of particular diamagnetic substances includewood, water, organic compounds (such as petroleum), metals (includingcopper, mercury, gold, bismuth), or benzoic acid.

In one particular example, skin abrasion for superficial resurfacing(e.g., microdermabrasion) can be used to treat acne, scars,hyperpigmentation, and other skin blemishes, as described herein.Microscissuining creates microchannels in the skin by eroding the outerlayers of skin with sharp microscopic metal granules (CarlisleScientific, Carlisle, Mass.), and Med Pharm Ltd (Charlbury, UK) hasdeveloped a novel dermal abrasion device (D3S) for the delivery ofdifficult to formulate therapeutics ranging from hydrophilic lowmolecular weight compounds to other biopharmaceuticals, and can beutilized in conjunction with administration of at least one therapeuticcomposition described herein. (See e.g., Roberts, et al., Clin. Exp.Pharmacol. Physiol. vol. 24, pp. 874-9 (1997); Murthy, et al., J.Controlled Rel. vol. 93, pp. 49-57 (2003); each of which is incorporatedherein by reference).

In at least one embodiment, Rathbone et al. have described artificialvesicles that mimic cell vesicles (such as TRANSFERSOMES®, from IDEA AG,Germany) can be utilized for administration of one or more therapeuticcomposition described herein. Artificial vesicles penetrate the skinbarrier along the transcutaneous moisture gradient and causes “virtual”pores between the cells in an organ without affecting its biologicalproperties. (See, e.g., Modified Release Drug Delivery Technology, NY,Marcel Dekker, Inc., vol. 126, pp. 471-619 (2004), which is incorporatedherein by reference). In addition, liposomes, and niosomes also serve ascarriers and can be utilized in administration of at least onetherapeutic composition described herein.

In at least one embodiment, the one or more frozen particles aregenerated by spraying a jet or mist of the composition constituents intoa low temperature environment (solid, liquid, gas, or any combinationthereof) such that the compositions freeze and form frozen particles. Inat least one embodiment, streams of frozen particles are extruded at lowtemperatures through fine ducts and into a low temperature environment.In at least one embodiment, the one or more frozen particles arepropelled through a nozzle or other delivery apparatus. In at least oneembodiment, the one or more frozen particles are delivered by utilizingflash boiling of a cold liquid. In one particular example, liquidnitrogen is flash boiled in order to accelerate, eject, or propel one ormore frozen particles for delivery or administration to at least onecell, tissue, or subject. In at least one embodiment, the flash boilingis caused or enhanced by one or more laser pulses (e.g., an infraredlaser pulse). In at least one embodiment, the one or more frozenparticles are prepared, delivered, or administered by another means.

In at least one embodiment, the at least one composition is propelledusing a pressure set at least about 1 psi, about 5 psi, about 10 psi,about 20 psi, about 30 psi, about 40 psi, about 50 psi, at least about100 psi, at least about 200 psi, at least about 300 psi, at least about400 psi, at least about 450 psi, at least about 500 psi, at least about600 psi, at least about 700 psi, at least about 800 psi, at least about900 psi, at least about 1000 psi, at least about 1100 psi, at leastabout 1200 psi, at least about 1300 psi, at least about 1400 psi, atleast about 1500 psi, about 2000 psi, about 2500 psi, about 3000 psi,about 3500 psi, about 4000 psi, about 5000 psi, about 6000 psi, about7000 psi, about 8000 psi, about 9000 psi, about 10000 psi, about 20000psi, about 30000 psi, about 40000 psi, about 50000 psi, or any valuetherebetween.

In at least one embodiment, the at least one composition is propelled toor at a predetermined velocity for delivery of the at least onecomposition to a desired location of the at least one biological tissue.In at least one embodiment, the at least one composition is propelled toor at a velocity of approximately 1 m/s, approximately 5 m/s,approximately 10 m/s, approximately 20 m/s, approximately 30 m/s,approximately 40 m/s, approximately 50 m/s, approximately 60 m/s,approximately 70 m/s, approximately 80 m/s, approximately 90 m/s,approximately 100 m/s, approximately 200 m/s, approximately 300 m/s,approximately 400 m/s, approximately 500 m/s, approximately 600 m/s,approximately 700 m/s, approximately 800 m/s, approximately 900 m/s,approximately 1000 m/s, approximately 1500 m/s, approximately 2000 m/s,approximately 3000 m/s, approximately 4000 m/s, approximately 5000 m/s,or any value greater or therebetween.

In at least one embodiment, the at least one composition is acceleratedor ejected toward the at least one biological tissue to a velocity ofapproximately 1 m/s, approximately 5 m/s, approximately 10 m/s,approximately 20 m/s, approximately 30 m/s, approximately 40 m/s,approximately 50 m/s, approximately 60 m/s, approximately 70 m/s,approximately 80 m/s, approximately 90 m/s, approximately 100 m/s,approximately 200 m/s, approximately 300 m/s, approximately 400 m/s,approximately 500 m/s, approximately 600 m/s, approximately 700 m/s,approximately 800 m/s, approximately 900 m/s, approximately 1000 m/s,approximately 1500 m/s, approximately 2000 m/s, approximately 3000 m/s,approximately 4000 m/s, approximately 5000 m/s, or any value greater ortherebetween.

In at least one embodiment, delivering at least one composition to atleast one biological tissue includes accelerating, ejecting, orpropelling a plurality of frozen particles toward the at least onebiological tissue. Such a plurality of particles may include at leastone embodiment wherein two or more frozen particles of the pluralityinclude one or more similar therapeutic agents. Likewise, a plurality offrozen particles may include at least one embodiment wherein two or morefrozen particles include one or more dissimilar therapeutic agents.

As described herein, a plurality of compositions or frozen particles mayinclude one or more subsets, which may be delivered or administered inan order of operations. In at least one embodiment, the order ofoperations includes delivery or administration in a pattern. In at leastone embodiment, the order of operations includes delivery oradministration in a predetermined pattern. In at least one embodiment,the order of operations includes delivery or administration insequential order. In at least one embodiment, the order of operationsincludes delivery or administration at random.

In at least one embodiment, delivering at least one composition to atleast one surface of at least one biological tissue of a subjectincludes contacting the at least one surface of at least one biologicaltissue of a subject with the composition. In at least one embodiment,delivering at least one composition to at least one surface of at leastone biological tissue of a subject includes contacting the at least onesurface of at least one biological tissue of a subject with the one ormore frozen particles. In at least one embodiment, delivering at leastone composition to at least one surface of at least one biologicaltissue of a subject includes rupturing one or more cells of at least onesurface of at least one biological tissue of a subject with the one ormore frozen particles.

In at least one embodiment, a method described herein includesextracting or collecting material from the at least one abraded surfaceof at least one biological tissue. Such extraction or collection mayinclude the use of at least one vacuum, aspirator, container,instrument, tool, device, chemical, laser, stylet, cannula, lightsource, scope (e.g., laprascope), needle, scalpel, shunt, stent, bag,film, filter, suction apparatus, tube, compressed gas, fluid (e.g.,fluid stream or mist), magnifying apparatus, imaging device, computingdevice, or system.

In at least one embodiment, at least one of the needle, scalpel, orother tools or instruments utilized in extracting or collecting materialfrom the at least one cell, tissue, or subject, includes one or morefrozen particles (e.g., frozen hydrogen oxide, or other agents asdescribed herein). Thus, the one or more frozen particles are fashionedor molded for use as microneedles or other instruments (e.g., scapels,blades, tools, etc.). In at least one embodiment, the one or more frozenparticles are utilized prior to, during, or subsequent to surgery.

In at least one embodiment, the extracted or collected material includesat least one organic or inorganic material. In at least one embodiment,the material includes one or more cells from the at least one abradedsurface of at least one biological tissue. In at least one embodiment,the at least one material includes at least part of one or moregranuloma, eschar, callus, atheromatous plaque, abscess, pustule,scaling (e.g., psoriasis or eczema), infected tissue, microorganismaccumulation, blood clot, blood vessel obstruction, duct obstruction,bowel obstruction, necrotic tissue, stratum corneum, hair follicle,nevus, wrinkle, keloid, biofilm, calculus, plaque, tartar, dandruff,keratin, collagen, dust, dirt, metal, glass, hair or fur, cellularsecretion, microorganism, blood cell, particulate matter, or connectivetissue.

In at least one embodiment, the at least one biological tissue islocated in at least one of in situ, in vitro, in vivo, in utero, inplanta, in silico, or ex vivo. In at least one embodiment, the at leastone biological tissue is located in vivo. In at least one embodiment,the at least one biological tissue is located in at least one tissue ororgan related to transplantation. In at least one embodiment,transplantation includes extraction or implantation of the at least onetissue or organ. In at least one embodiment, the at least one tissue ororgan related to transplantation is extracted from at least one firstbiological source or subject and implanted into at least one secondbiological source or subject. In at least one embodiment, the at leastone tissue or organ related to transplantation is cultured prior toimplantation in a subject. In at least one embodiment, the tissue ororgan related to transplantation is an artificial tissue or organ (e.g.a bladder, heart, kidney, liver, pancreas, skin, eye, lung, nerve, bloodvessel, and others). In at least one embodiment, the tissue or organrelated to transplantation involves at least two sources (i.e. multiplespecies, partially artificial or synthetic, multiple biological cells ortissues including stem cells). In at least one embodiment, the at leastone tissue or organ related to transplantation includes at least onedonor or recipient tissue or organ. In at least one embodiment, the atleast one donor includes at least one cadaver. In at least oneembodiment, the at least one biological tissue is ingested by at leastone subject.

In at least one embodiment, the at least one tissue or organ related totransplantation includes one or more cells. The one or more cells mayinclude endogenous or exogenous cells relative to a particular subject.In at least one embodiment, the at least one tissue or organ related totransplantation relates to one or more stem cells (e.g., hematopoieticstem cells, adipocyte stem cells, neuronal stem cells, embryonic stemcells, hepatic stem cells, dermal stem cells, pancreatic stem cells,stem cells related to bone, stem cells related to muscle, or others). Inat least one embodiment, the at least one tissue or organ related totransplantation includes one or more of skin, scalp, hair, nail, nailbed, teeth, eye, cornea, ear, ovary, oviduct, tongue, tonsil, adenoid,liver, bone, pancreas, stomach, blood vessel, blood, lymph, heart, heartvalve, lung, brain, breast, kidney, bladder, urethra, ureter, gallbladder, uterus, prostate, testes, vas deferens, fallopian tubes, largeintestine, small intestine, esophagus, oral cavity, nasal cavity, oticcavity, tendon, vein (e.g., femoral or saphenous vein), artery,capillary, connective tissue, muscle tissue, or adipose tissue.

In at least one embodiment, the at least one biological tissue includesat least one cell mass. In at least one embodiment, the at least onecell mass includes at least one of a scar, pore, pit, eschar, granuloma,keloid, artheromatous plaque, abscess, pustule, scaling (e.g., psoriasisor eczema), infected tissue, hair follicle, necrotic tissue, stratumcorneum, wrinkle, wound, tumor, skin structure, nevus, cyst, lesion,callus, neoplastic tissue, gangrenous tissue, or cellular deposit. In atleast one embodiment, the at least one cell mass includes at least onebenign or malignant tumor. In at least one embodiment, the at least onebenign or malignant tumor relates to one or more of a melanoma,lymphoma, leukemia, sarcoma, blastoma, or carcinoma.

In at least one embodiment, the at least one cell mass is related to atleast one blood clot, microorganism accumulation, blood vesselobstruction, duct obstruction, bowel obstruction, infection, gangrene,connective tissue destruction, tissue or organ damage, injury, whiteblood cell accumulation, or cancer.

For embodiments described herein, those having skill in the art willrecognize that the state of the art has progressed to the point wherethere is little distinction left between hardware, software, and/orfirmware implementations of aspects of systems; the use of hardware,software, and/or firmware is generally (but not always, in that incertain contexts the choice between hardware and software can becomesignificant) a design choice representing cost vs. efficiency tradeoffs.Those having skill in the art will appreciate that there are variousvehicles by which processes and/or systems and/or other technologiesdescribed herein can be effected (e.g., hardware, software, and/orfirmware), and that the preferred vehicle will vary with the context inwhich the processes and/or systems and/or other technologies aredeployed. For example, if an implementer determines that speed andaccuracy are paramount, the implementer may opt for a mainly hardwareand/or firmware vehicle; alternatively, if flexibility is paramount, theimplementer may opt for a mainly software implementation; or, yet againalternatively, the implementer may opt for some combination of hardware,software, and/or firmware. Hence, there are several possible vehicles bywhich the processes and/or devices and/or other technologies describedherein may be effected, none of which is inherently superior to theother in that any vehicle to be utilized is a choice dependent upon thecontext in which the vehicle will be deployed and the specific concerns(e.g., speed, flexibility, or predictability) of the implementer, any ofwhich may vary. Those skilled in the art will recognize that opticalaspects of implementations will typically employ optically-orientedhardware, software, and or firmware.

In some implementations described herein, logic and similarimplementations may include software or other control structures.Electronic circuitry, for example, may have one or more paths ofelectrical current constructed and arranged to implement variousfunctions as described herein. In some implementations, one or moremedia may be configured to bear a device-detectable implementation whensuch media hold or transmit device detectable instructions operable toperform as described herein. In some variants, for example,implementations may include an update or modification of existingsoftware or firmware, or of gate arrays or programmable hardware, suchas by performing a reception of or a transmission of one or moreinstructions in relation to one or more operations described herein.Alternatively or additionally, in some variants, an implementation mayinclude special-purpose hardware, software, firmware components, and/orgeneral-purpose components executing or otherwise invokingspecial-purpose components. Specifications or other implementations maybe transmitted by one or more instances of tangible transmission mediaas described herein, optionally by packet transmission or otherwise bypassing through distributed media at various times.

Alternatively or additionally, implementations may include executing aspecial-purpose instruction sequence or invoking circuitry for enabling,triggering, coordinating, requesting, or otherwise causing one or moreoccurrences of virtually any functional operations described herein. Insome variants, operational or other logical descriptions herein may beexpressed as source code and compiled or otherwise invoked as anexecutable instruction sequence. In some contexts, for example, C++ orother code sequences can be compiled or implemented in high-leveldescriptor languages (e.g., a logic-synthesizable language, a hardwaredescription language, a hardware design simulation, and/or other suchsimilar mode(s) of expression). For example, some or all of the logicalexpression may be manifested as a Verilog-type hardware description orother circuitry model before physical implementation in hardware. Thoseskilled in the art will recognize how to obtain, configure, and optimizesuitable transmission or computational elements, material supplies,actuators, or other structures in light of these teachings.

As indicated in FIGS. 7-9, at least one embodiment, a method 700includes comparing 710 information regarding at least one aspect ofadministering at least one frozen particle therapeutic composition to atleast one subject and information regarding at least one clinicaloutcome following receipt by the at least one subject of at least onefrozen particle therapeutic composition; and providing outputinformation optionally based on the comparison.

In at least one embodiment, the method includes determining at least onestatistical correlation 720. In at least one embodiment, the methodincludes counting the occurrence of at least one clinical outcome 730.In at least one embodiment, the method includes determining at least onecorrelation before the administration of the at least one frozenparticle therapeutic composition 735. In at least one embodiment,information regarding at least one aspect of administering at least onefrozen particle therapeutic composition includes information regardingthe amount of at least one frozen particle therapeutic composition ortherapeutic agent administered to at least one biological tissue of asubject 740. In at least one embodiment, the information regarding atleast one aspect of administering or delivering at least one frozenparticle therapeutic composition includes information regarding at leastone dimension of biological tissue penetration 750. In at least oneembodiment, information regarding the at least one dimension ofbiological tissue penetration includes information regarding at leastone of depth, width, or breadth of administration of at least one frozenparticle therapeutic composition to at least one biological tissue of atleast one subject 760.

In at least one embodiment, the information regarding at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information regarding two or more subjects with oneor more common attributes 770. In at least one embodiment, the one ormore common attributes include genetic attributes, mental attributes, orpsychological attributes 780. In at least on embodiment, the one or morecommon attributes include genotype attributes or phenotype attributes790.

In at least one embodiment, the one or more common attributes 797include at least one of height; weight; medical diagnosis; familialbackground; results on one or more medical tests; ethnic background;body mass index; age; presence or absence of at least one disease orcondition; species; ethnicity; race; allergies; gender; thickness ofepidermis; thickness of dermis; thickness of stratum corneum; keratindeposition; collagen deposition; blood vessel condition; skin condition;hair or fur condition; muscle condition; tissue condition; organcondition; nerve condition; brain condition; presence or absence of atleast one biological, chemical, or therapeutic agent in the subject;pregnancy status; lactation status; genetic profile; proteomic profile;partial or whole genetic sequence; partial or whole proteomic sequence;medical history; lymph condition, or blood condition.

In at least one embodiment, the output information 810 includes at leastone of a response signal, a comparison code, a comparison plot, adiagnostic code, a treatment code, a test code, a code indicative of atleast one treatment received, a code indicative of at least oneprescribed treatment step, a code indicative of at least one vaccinationdelivered; a code indicative of at least one therapeutic agentdelivered; a code indicative of at least one diagnostic agent delivered;a code indicative of at least one interaction of a delivered agent andat least one biological or chemical agent in the subject; a codeindicative of at least one dispersion or location of at least onedelivered agent; a code indicative of at least one detection materialdelivered; a code indicative of the depth of penetration of a deliveredagent; or a code indicative of the condition of at least one location ofan administered or delivered frozen particle composition. In at leastone embodiment, the at least one aspect of cellular or tissue abrasionor ablation includes information regarding at least one cellular ortissue source 820. In at least one embodiment, the information regardingat least one tissue source includes information regarding at least oneabnormal cellular or tissue source 830. In at least one embodiment, theinformation regarding at least one cellular or tissue source includesinformation regarding at least one type of cell or tissue 840. In atleast one embodiment, the cellular or tissue source includes at leastone cell or biological tissue described herein.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one of nitrogen, carbondioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,bromine, oxygen, air, argon, polyethylene glycol, acetone, ethylacetate, dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon,.methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether 850.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one major dimension ofapproximately one decimeter or less, or approximately one centimeter orless, approximately one millimeter or less, approximately one micrometeror less, approximately one nanometer or less, or any value therebetween860.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes one or more reinforcement agents870. In at least one embodiment, the at least one frozen particlecomposition or therapeutic composition includes one or more explosivematerials 880. In at least one embodiment, the receipt by the at leastone subject of at least one frozen particle composition or therapeuticcomposition is pursuant to at least one clinical trial 900.

In at least one embodiment, the method includes creating at least oneinclusion criterion and at least one exclusion criterion for a clinicaltrial involving the at least one frozen particle composition ortherapeutic composition 910. In at least one embodiment, the methodfurther comprises suggesting the inclusion of one or more of the atleast one subject in at least one clinical trial 920. In at least oneembodiment, the method further comprises suggesting the exclusion of oneor more of the at least one subject in at least one clinical trial 930.In certain instances, multiple subjects from multiple clinical trialsare included. In at least one embodiment, the method further includesusing one or more of the at least one comparison to predict at least oneclinical outcome regarding at least one second subject 940. In at leastone embodiment, the at least one second subject has not received the atleast one frozen particle composition or therapeutic composition 950. Inat least one embodiment, the at least one second subject is a pluralityof people; and the method further comprises segregating subjectidentifiers associated with the plurality of people in reference to thepredicted at least one clinical outcome 960. In at least one embodiment,the at least one second subject is a plurality of people; and the methodfurther comprises determining the eligibility of the at least one secondsubject for the at least one clinical trial 970.

As indicated in FIGS. 10-12, at least one aspect includes a method 1000relating to predicting a clinical outcome of administering at least onefrozen particle therapeutic composition to at least one biologicaltissue of at least one first subject includes determining a similarityor a dissimilarity in information regarding at least one aspect ofadministering at least one therapeutic composition to the at least onebiological tissue of the at least one first subject to informationregarding at least one aspect of administering at least one therapeuticcomposition to the at least one biological tissue of the at least onesecond subject, wherein the at least one second subject attained aclinical outcome following receipt of the at least one frozen particletherapeutic composition; and providing output information optionallybased on the determination 1010.

In at least one embodiment, the information regarding the at least oneaspect of administering at least one frozen particle therapeuticcomposition includes information 1020 regarding the amount of at leastone frozen particle therapeutic composition or therapeutic agentdelivered to at least one biological tissue of a subject. In at leastone embodiment, the information regarding the at least one aspect ofadministering at least one frozen particle therapeutic compositionincludes information 1030 regarding at least one dimension of biologicaltissue penetration. In at least one embodiment, the informationregarding the at least one dimension of biological tissue penetrationincludes information 1040 regarding at least one of depth, width, orbreadth of delivery of at least one frozen particle therapeuticcomposition to at least one biological tissue of at least one subject;or information 1050 regarding two or more subjects with commonattributes.

In at least one embodiment, the one or more common attributes includegenetic attributes, mental attributes, or psychological attributes 1060.In at least on embodiment, the one or more common attributes includegenotype attributes or phenotype attributes 1070.

In at least one embodiment, the one or more common attributes 1080include at least one of height; weight; medical diagnosis; familialbackground; results on one or more medical tests; ethnic background;body mass index; age; presence or absence of at least one disease orcondition; species; ethnicity; race; allergies; gender; thickness ofepidermis; thickness of dermis; thickness of stratum corneum; keratindeposition; collagen deposition; blood vessel condition; skin condition;hair or fur condition; muscle condition; tissue condition; organcondition; nerve condition; brain condition; presence or absence of atleast one biological, chemical, or therapeutic agent in the subject;pregnancy status; lactation status; genetic profile; proteomic profile;partial or whole genetic sequence; medical history; partial or wholeproteomic sequence; lymph condition, or blood condition.

In at least one embodiment, the output information 1100 includes atleast one of a response signal, a comparison code, a comparison plot, adiagnostic code, a treatment code, a test code, a code indicative of atleast one treatment received, a code indicative of at least oneprescribed treatment step, a code indicative of at least one vaccinationdelivered; a code indicative of at least one therapeutic agentdelivered; a code indicative of at least one diagnostic agent delivered;a code indicative of at least one interaction of a delivered agent andat least one biological or chemical agent in the subject; a codeindicative of at least one dispersion or location of at least onedelivered agent; a code indicative of at least one detection materialdelivered; a code indicative of the depth of penetration of a deliveredagent; or a code indicative of the condition of at least one location ofan administered or delivered frozen particle composition or therapeuticcomposition. In at least one embodiment, the at least one aspect ofcellular or tissue abrasion or ablation includes information regardingat least one cellular or tissue source 1110. In at least one embodiment,the information regarding at least one tissue source includesinformation regarding at least one abnormal cellular or tissue source1120. In at least one embodiment, the information regarding at least onecellular or tissue source includes information regarding at least onetype of cell or tissue 1130. In at least one embodiment, the cellular ortissue source includes at least one cell or biological tissue describedherein.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one of nitrogen, carbondioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,bromine, oxygen, air, argon, polyethylene glycol, acetone, ethylacetate, dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether 1140.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one major dimension ofapproximately one decimeter or less, or approximately one centimeter orless, approximately one millimeter or less, approximately one micrometeror less, approximately one nanometer or less, or any value therebetween1150.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes one or more reinforcement agents1160. In at least one embodiment, the at least one frozen particlecomposition or therapeutic composition includes one or more explosivematerials 1170.

In at least one embodiment, the receipt by the at least one subject ofat least one frozen particle composition or therapeutic composition ispursuant to at least one clinical trial 1200. In at least oneembodiment, the method further comprises determining at least onecorrelation before the administration or delivery of the at least onefrozen particle composition or therapeutic composition to at least onesubject 1210. The at least one subject includes, but is not limited toat least one subject described herein.

In at least one embodiment, the method includes creating at least oneinclusion criterion and at least one exclusion criterion for a clinicaltrial involving the at least one frozen particle composition ortherapeutic composition 1220. In at least one embodiment, the methodfurther comprises suggesting the inclusion of one or more of the atleast one subject in at least one clinical trial 1230. In at least oneembodiment, the method further comprises suggesting the exclusion of oneor more of the at least one subject in at least one clinical trial 1240.In certain instances, multiple subjects from multiple clinical trialsare included. In at least one embodiment, the method further includesusing one or more of the at least one comparison to predict at least oneclinical outcome regarding at least one second subject 1250. In at leastone embodiment, the at least one second subject has not received the atleast one frozen particle composition or therapeutic composition 1260.In at least one embodiment, the method includes predicting at least oneclinical outcome involving the at least one second subject, and the atleast one second subject is a plurality of people; and the methodfurther comprises segregating subject identifiers associated with theplurality of people in reference to the predicted at least one clinicaloutcome 1270.

In at least one embodiment, the at least one second subject is aplurality of people; and the method further comprises determining theeligibility of the at least one second subject for the at least oneclinical trial 1280.

As shown in FIGS. 13-15, at least one embodiment includes a system 1300including at least one computer program 1310, configured with acomputer-readable medium, for use with at least one computer system andwherein the computer program includes a plurality of instructionsincluding but not limited to one or more instructions 1320 for comparinginformation regarding at least one aspect of at least one therapeuticadministration of at least one frozen particle composition ortherapeutic composition to at least one subject. In at least oneembodiment, information 1330 regarding amount of the at least one frozenparticle composition, therapeutic composition, or therapeutic agentadministered to at least one biological tissue of at least one subject.In at least one embodiment, information regarding at least one aspect ofat least one therapeutic administration of at least one frozen particlecomposition or therapeutic composition includes information regarding atleast one dimension of biological tissue penetration 1340. In at leastone embodiment, information regarding at least one aspect of at leastone therapeutic administration of at least one frozen particlecomposition or therapeutic composition includes information regarding atleast one of depth, width, or breadth of administration of at least onefrozen particle composition or therapeutic composition to at least onebiological tissue of at least one subject 1350. In at least oneembodiment, information regarding at least one aspect of at least onetherapeutic administration includes information regarding two or moresubjects with one or more common attributes 1360. In at least oneembodiment, the computing device is configured to communicate with atleast one imaging device. In at least one embodiment, the computingdevice is configured to communicate with at least one printing device.In at least one embodiment, the computing device is configured tocommunicate with at least one input device 1370.

In at least one embodiment, the information regarding at least oneaspect of therapeutic administration of at least one therapeuticcomposition includes information regarding at least one cellular ortissue source 1400; information regarding at least one abnormal cellularor tissue source 1410; or information regarding at least one type ofcell or tissue 1420. In at least one embodiment, at least one frozenparticle composition or therapeutic composition includes at least one ofnitrogen, carbon dioxide, hydrogen oxide, helium, neon, xenon, krypton,chlorine, bromine, oxygen, air or argon. In at least one embodiment, theat least one frozen particle composition or therapeutic compositionincludes at least one of polyethylene glycol, acetone, ethyl acetate,dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether 1430. In atleast one embodiment, at least one frozen particle composition ortherapeutic composition includes at least one major dimension ofapproximately one decimeter or less, approximately one centimeter orless, approximately one millimeter or less, approximately one micrometeror less, approximately one nanometer or less, or any value therebetween1440. In at least one embodiment, the at least one frozen particlecomposition or therapeutic composition includes one or morereinforcement agents 1450 or one or more explosive materials 1460.

In at least one embodiment, the receipt by the at least one subject ofat least one frozen particle composition or therapeutic composition ispursuant to at least one clinical trial 1500. In at least oneembodiment, the system further comprises determining at least onecorrelation before the delivery or administration of the at least onefrozen particle composition or therapeutic composition to at least onesubject 1510.

In at least one embodiment, the method includes creating at least oneinclusion criterion and at least one exclusion criterion for a clinicaltrial involving the at least one frozen particle composition ortherapeutic composition 1520. In at least one embodiment, theinstructions further comprise suggesting the inclusion of one or more ofthe at least one subject in at least one clinical trial 1530. In certaininstances, multiple subjects from multiple clinical trials are included.

In at least one embodiment, the instructions include suggesting theexclusion of one or more of the at least one subject in at least oneclinical trial 1540.

In at least one embodiment, a method includes using one or more of theat least one comparison to predict at least one clinical outcomeregarding at least one second subject 1550. In at least one embodiment,the at least one second subject has not received the at least one frozenparticle composition or therapeutic composition 1560. In at least oneembodiment, the at least one second subject is a plurality of people;and further comprising segregating subject identifiers associated withthe plurality of people in reference to the predicted at least oneclinical outcome 1570.

In at least one embodiment, the using one or more of the at least onecomparison, wherein the at least one second subject is a plurality ofpeople; and further comprising determining the eligibility of the atleast one second subject for the at least one clinical trial 1580.

As indicated in FIG. 16, at least one embodiment relates to a system1600 including at least one computer program 1610 configured with acomputer-readable medium, for use with at least one computer system andwherein the computer program includes a plurality of instructionsincluding but not limited to one or more instructions 1620 for comparinginformation regarding at least one aspect of at least one therapeuticadministration of at least one frozen particle therapeutic compositionto at last one subject, and information regarding at least one frozenparticle therapeutic composition involving at least one biologicaltissue of at least one subject; and one or more instructions forapplying one or more comparisons to the information regarding the atleast one aspect of therapeutic administration of at least one frozenparticle therapeutic composition to a plurality of people. In at leastone embodiment, the computer program includes one or more instructions1630 for segregating subject identifiers associated with the pluralityof people in reference to at least one of the one or more appliedcomparisons. In at least one embodiment, information regarding at leastone aspect of at least one therapeutic administration includesinformation 1640 regarding the amount of at least one frozen particlecomposition, therapeutic composition or therapeutic agent administeredto at least one biological tissue of at least one subject; information1650 regarding at least one dimension of biological tissue penetration;information 1660 regarding at least one of depth, width, or breadth ofadministration of at least one frozen particle therapeutic compositionto at least one biological tissue of at least one subject. In at leastone embodiment, the computer program includes one or more instructions1670 for segregating individual identifiers associated with theplurality of people in reference to at least one characteristic sharedby two or more subjects in the plurality of people.

As shown in FIG. 17, at least one embodiment relates to a computerprogram product 1700 that includes a signal bearing medium 1710 bearingat least one of one or more instructions 1720 for receiving a firstinput associated with a first possible dataset, the first possibledataset including data representative of one or more measurementsrelating to one or more physical attributes of a first subject; one ormore instructions 1730 for comparing a value associated with the firstpossible dataset with a second dataset including values representativeof predictive regimen parameters from a second subject with one or moresimilar or dissimilar physical attributes; one or more instructions 1740for determining from the comparison at least one frozen particletherapeutic composition regimen for the first subject and outputinformation; one or more instructions 1750 for accessing the firstpossible dataset in response to the first input; one or moreinstructions 1760 for generating the first possible dataset in responseto the first input; one or more instructions 1770 for determining agraphical illustration of the first possible dataset; one or moreinstructions 1780 for determining a graphical illustration of the secondpossible dataset; and at least one generated output optionally based onthe determination.

In at least one embodiment, the computer program product includes asignal bearing medium that includes a computer-readable medium 1790. Inat least one embodiment, the signal bearing medium of the computerprogram product includes a recordable medium 1792. In at least oneembodiment, the computer program product includes a signal bearingmedium that includes a communications medium 1794.

As indicated in FIG. 18, at least one embodiment relates to a computerprogram product 1800 that includes a signal bearing medium 1810 bearingat least one of one or more instructions 1820 for processing a firstpossible dataset, the first possible dataset including datarepresentative of one or more measurements relating to one or morephysical attributes of a first subject; one or more instructions 1830for comparing a value associated with the first possible dataset with asecond dataset including values representative of predictive regimenparameters from a second subject with one or more similar or dissimilarphysical attributes; one or more instructions 1840 for determining fromthe comparison at least one frozen particle composition or therapeuticcomposition treatment regimen for the first subject, and outputinformation.

As indicated in FIG. 19, at least one embodiment relates to a computerprogram product 1900 that includes a signal bearing medium 1910 bearingat least one of one or more instructions 1920 responsive to a firstpossible dataset, the first possible dataset including datarepresentative of one or more measurements relating to one or morephysical attributes of a first subject; one or more instructions 1930for comparing a value associated with the first possible dataset with asecond dataset including values representative of predictive regimenparameters for a second subject with one or more similar or dissimilarphysical attributes; one or more instructions 1940 for determining fromthe comparison at least one frozen particle composition or therapeuticcomposition treatment regimen for the first subject; and outputinformation optionally based on the determination.

As shown in FIG. 20, at least one embodiment relates to a computerprogram product 2000 that includes a signal bearing medium 2010 bearingat least one of one or more instructions 2020 for receiving a firstinput associated with a first possible dataset, the first possibledataset including data representative of one or more measurementsrelating to one or more physical attributes of a subject; one or moreinstructions 2030 for comparing a value associated with the firstpossible dataset with a second dataset including values representativeof parameters relating to one or more expected biological changesfollowing administration of one or more frozen particle compositions ortherapeutic compositions; one or more instructions 2040 for determiningfrom the comparison at least one biological change followingadministration of one or more frozen particle compositions ortherapeutic compositions to the subject; at least one generated outputoptionally based on the determination.

In at least one embodiment, the computer program product includes one ormore instructions 2050 for accessing the first possible dataset inresponse to the first input. In at least one embodiment, the computerprogram product includes one or more instructions 2060 for generatingthe first possible dataset in response to the first input.

In at least one embodiment, the computer program product includes one ormore instructions 2070 for determining a graphical illustration of thefirst possible dataset. In at least one embodiment, the computer programproduct includes one or more instructions 2080 for determining agraphical illustration of the second possible dataset. In at least oneembodiment, the signal bearing medium includes a computer-readablemedium 2090. In at least one embodiment, the signal bearing mediumincludes a recordable medium 2092. In at least one embodiment, thesignal bearing medium includes a communications medium 2094.

As indicated in FIG. 21, at least one embodiment a computer programproduct 2100 includes a signal bearing medium 2110 bearing at least oneof one or more instructions 2120 for processing a first input associatedwith a first possible dataset, the first possible dataset including datarepresentative of one or more measurements relating to one or morephysical attributes of a subject; one or more instructions 2130 forcomparing a value associated with the first possible dataset with asecond dataset including values representative of parameters relating toone or more expected biological changes following administration of oneor more frozen particle compositions or therapeutic compositions; one ormore instructions 2140 for determining from the comparison at least onebiological change following administration of one or more frozenparticle compositions or therapeutic compositions to the subject; atleast one generated output optionally based on the determination.

As shown in FIG. 22, at least one embodiment relates to a computerprogram product 2200 includes a signal bearing medium 2210 bearing atleast one of one or more instructions 2220 responsive to a firstpossible dataset, the first possible dataset including datarepresentative of one or more measurements relating to one or morephysical attributes of a subject; one or more instructions 2230 forcomparing a value associated with the first possible dataset with asecond dataset including values representative of parameters relating toone or more expected biological changes following administration of oneor more frozen particle compositions or therapeutic compositions; one ormore instructions 2240 for determining from the comparison at least onebiological change following administration of one or more frozenparticle compositions or therapeutic compositions to the subject; andoutput information optionally based on the determination.

As indicated in FIGS. 23-25, at least one embodiment, a method 2300includes comparing 2310 information regarding at least one aspect ofcellular or tissue abrasion or ablation of at least one biologicaltissue of at least one subject and information regarding at least oneclinical outcome following receipt by the at least one subject of atleast one frozen particle composition or therapeutic composition; andproviding output information optionally based on the determination. Inat least one embodiment, the method includes determining at least onestatistical correlation 2320. In at least one embodiment, the methodincludes counting the occurrence of at least one clinical outcome 2330.In at least one embodiment, the information regarding at least oneaspect of cellular or tissue abrasion or ablation includes informationregarding quantity of cells or tissue removed or destroyed 2340. In atleast one embodiment, the information regarding at least one aspect ofcellular or tissue abrasion or ablation includes information regardingat least one dimension of cellular or tissue removal or destruction, orremoval or destruction of other materials, such as plaque, extracellularmatrix, collagen, elastin, protein, or other materials 2350. In at leastone embodiment, information regarding the at least one dimension ofcellular removal or destruction includes information regarding at leastone of depth, width, or breadth of cellular removal or destruction 2360.

In at least one embodiment, the information regarding at least oneaspect of cellular or tissue abrasion or ablation includes informationregarding two or more subjects with one or more common attributes 2370.In at least one embodiment, the one or more common attributes includegenetic attributes, mental attributes, or psychological attributes 2380.In at least on embodiment, the one or more common attributes includegenotype attributes or phenotype attributes 2390.

In at least one embodiment, the one or more common attributes 2397include at least one of height; weight; medical diagnosis; familialbackground; results on one or more medical tests; ethnic background;body mass index; age; presence or absence of at least one disease orcondition; species; ethnicity; race; allergies; gender; thickness ofepidermis; thickness of dermis; thickness of stratum corneum; keratindeposition; collagen deposition; blood vessel condition; skin condition;hair or fur condition; muscle condition; tissue condition; organcondition; nerve condition; brain condition; presence or absence of atleast one biological, chemical, or therapeutic agent in the subject;pregnancy status; lactation status; genetic profile; proteomic profile;partial or whole genetic sequence; medical history; partial or wholeproteomic sequence; lymph condition, or blood condition.

In at least one embodiment, the output information 2410 includes atleast one of a response signal, a comparison code, a comparison plot, adiagnostic code, a treatment code, a test code, a code indicative of atleast one treatment received, a code indicative of at least oneprescribed treatment step, a code indicative of at least one vaccinationdelivered; a code indicative of at least one therapeutic agentdelivered; a code indicative of at least one diagnostic agent delivered;a code indicative of at least one interaction of a delivered agent andat least one biological or chemical agent in the subject; a codeindicative of at least one dispersion or location of at least onedelivered agent; a code indicative of at least one detection materialdelivered; a code indicative of the depth of penetration of a deliveredagent; or a code indicative of the condition of at least one location ofa delivered or administered frozen particle composition. In at least oneembodiment, the at least one aspect of cellular or tissue abrasion orablation includes information regarding at least one cellular or tissuesource 2420. In at least one embodiment, the information regarding atleast one tissue source includes information regarding at least oneabnormal cellular or tissue source 2430. In at least one embodiment, theinformation regarding at least one cellular or tissue source includesinformation regarding at least one type of cell or tissue 2440. In atleast one embodiment, the cellular or tissue source includes at leastone cell or biological tissue described herein.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one of nitrogen, carbondioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,bromine, oxygen, air, argon, polyethylene glycol, acetone, ethylacetate, dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether 2450.

In at least one embodiment, the at least one frozen particle compositionincludes at least one major dimension of approximately one decimeter orless, or approximately one centimeter or less, approximately onemillimeter or less, approximately one micrometer or less, approximatelyone nanometer or less, or any value therebetween 2460.

In at least one embodiment, the at least one frozen particle compositionincludes one or more reinforcement agents 2470. In at least oneembodiment, the at least one frozen particle composition includes one ormore explosive materials 2480. In at least one embodiment, the receiptby the at least one subject of at least one frozen particle compositionis pursuant to at least one clinical trial 2500. In at least oneembodiment, the method further comprises determining at least onecorrelation 2510 before the delivery or administration of the at leastone frozen particle composition to at least one subject. The at leastone subject includes, but is not limited to at least one subjectdescribed herein.

In at least one embodiment, the method includes creating at least oneinclusion criterion and at least one exclusion criterion for a clinicaltrial involving the at least one frozen particle composition ortherapeutic composition 2515. In at least one embodiment, the methodfurther comprises suggesting the inclusion of one or more of the atleast one subject in at least one clinical trial 2520. In at least oneembodiment, the method further comprises suggesting the exclusion of oneor more of the at least one subject in at least one clinical trial 2530.In certain instances, multiple subjects from multiple clinical trialsare included. In at least one embodiment, the method further includesusing one or more of the at least one correlation to predict at leastone clinical outcome regarding at least one second subject 2540. In atleast one embodiment, the at least one second subject has not receivedthe at least one frozen particle composition or therapeutic composition2550. In at least one embodiment, the method further comprisespredicting at least one clinical outcome involving the at least onesecond subject, wherein the at least one second subject is a pluralityof people; and segregating subject identifiers associated with theplurality of people in reference to the predicted at least one clinicaloutcome 2560. In at least one embodiment, the at least one secondsubject is a plurality of people; and the method further comprisesdetermining the eligibility of the at least one second subject for theat least one clinical trial 2570.

As indicated in FIGS. 26-28, at least one embodiment relates to a method2600 of predicting a clinical outcome of at least one frozen particlecomposition treatment for at least one first subject includesdetermining 2610 a similarity or a dissimilarity in informationregarding at least one aspect of cellular or tissue abrasion or ablationof at least one biological tissue of at least one first subject toinformation regarding at least one aspect of cellular or tissue abrasionor ablation of at least one biological tissue of at least one secondsubject, wherein the at least one second subject attained a clinicaloutcome following receipt of the at least one frozen particlecomposition or therapeutic composition; and providing output informationoptionally based on the determination.

In at least one embodiment, the information regarding at least oneaspect of cellular or tissue abrasion or ablation includes informationregarding the quantity of cells or tissue removed or destroyed 2620. Inat least one embodiment, the information regarding at least one aspectof cellular or tissue abrasion or ablation includes informationregarding at least one dimension of cellular, tissue, or other materialremoval or destruction 2630. In at least one embodiment, the at leastone dimension of cellular removal or destruction includes informationregarding at least one of depth, width, or breadth of cellular removalor destruction 2640. In at least one embodiment, the informationregarding at least one aspect of cellular or tissue abrasion or ablationincludes information regarding two or more subjects with one or morecommon attributes 2650.

In at least one embodiment, the one or more common attributes includebut are not limited to genetic attributes, mental attributes, orpsychological attributes 2660. In at least one embodiment, the one ormore common attributes include genotype attributes or phenotypeattributes 2670.

In at least one embodiment, the one or more common attributes include atleast one of height; weight; medical diagnosis; familial background;results on one or more medical tests; ethnic background; body massindex; age; presence or absence of at least one disease or condition;species; ethnicity; race; allergies; gender; thickness of epidermis;thickness of dermis; thickness of stratum corneum; keratin deposition;collagen deposition; blood vessel condition; skin condition; hair or furcondition; muscle condition; tissue condition; organ condition; nervecondition; brain condition; presence or absence of at least onebiological, chemical, or therapeutic agent in the subject; pregnancystatus; lactation status; medical history; genetic profile; proteomicprofile; partial or whole genetic sequence; partial or whole proteomicsequence; lymph condition, medical history, or blood condition 2680.

In at least one embodiment, the output information includes at least oneof a response signal, a comparison code, a comparison plot, a diagnosticcode, a treatment code, a test code, a code indicative of at least onetreatment received, a code indicative of at least one prescribedtreatment step, a code indicative of at least one vaccination delivered;a code indicative of at least one therapeutic agent delivered; a codeindicative of at least one diagnostic agent delivered; a code indicativeof at least one interaction of a delivered agent and at least onebiological or chemical agent in the subject; a code indicative of atleast one dispersion or location of at least one delivered agent; a codeindicative of at least one detection material delivered; a codeindicative of the depth of penetration of a delivered agent; or a codeindicative of the condition of at least one location of a delivered oradministered frozen particle composition 2700.

In at least one embodiment, the information regarding at least oneaspect of cellular or tissue abrasion or ablation includes informationregarding at least one cellular or tissue source 2710. In at least oneembodiment, the cellular or tissue source includes but is not limited toat least one biological tissue or cell described herein. In at least oneembodiment, the information regarding at least one tissue sourceincludes information regarding at least one abnormal cellular or tissuesource 2720. In at least one embodiment, the information regarding atleast one cellular or tissue source includes information regarding atleast one type of cell or tissue 2730. In at least one embodiment, theinformation regarding at least one aspect of cellular or tissue abrasionor ablation includes information regarding at least one type of cell ortissue.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one of nitrogen, carbondioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,bromine, oxygen, air or argon. In at least one embodiment, the at leastone frozen particle composition or therapeutic composition includes atleast one of polyethylene glycol, acetone, ethyl acetate, dimethylsulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether 2740.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one major dimension ofapproximately one decimeter or less, or approximately one centimeter orless, or approximately one millimeter or less, or approximately onemicrometer or less, or approximately one nanometer or less, or any valuetherebetween 2750.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes one or more reinforcement agents2760. In at least one embodiment, the at least one frozen particlecomposition or therapeutic composition includes one or more explosivematerials 2770.

In at least one embodiment, the receipt by the at least one subject ofat least one frozen particle composition or therapeutic composition ispursuant to at least one clinical trial 2800. In at least oneembodiment, the method includes creating at least one inclusioncriterion and at least one exclusion criterion for a clinical trialinvolving the at least one frozen particle composition or therapeuticcomposition 2810. In at least one embodiment, the method furthercomprises suggesting the inclusion of one or more of the at least onesubject in at least one clinical trial 2820. In certain instances,multiple subjects from multiple clinical trials are included. In atleast one embodiment, the method includes suggesting the exclusion ofone or more of the at least one subject in at least one clinical trial2830.

In at least one embodiment, a method includes using one or more of theat least one determination to predict at least one clinical outcomeregarding at least one second subject 2840. In at least one embodiment,the at least one second subject has not received the at least one frozenparticle composition or therapeutic composition 2850. In at least oneembodiment, the at least one second subject is a plurality of people;and the method further comprises segregating subject identifiersassociated with the plurality of people in reference to the predicted atleast one clinical outcome 2860.

In at least one embodiment, the using one or more of the at least onecomparison, wherein the at least one second subject is a plurality ofpeople; and the method further comprises determining the eligibility ofthe at least one second subject for the at least one clinical trial2870.

As indicated in FIGS. 29-30, at least one aspect relates to a system2900 that includes at least one computing device 2910; one or moreinstructions 2920 that when executed on the at least one computingdevice cause the at least one computing device to receive a first inputassociated with a first possible dataset, the first possible datasetincluding data representative of one or more measurements relating toone or more physical attributes of a first subject; one or moreinstructions 2930 that when executed on the at least one computingdevice cause the at least one computing device to compare a valueassociated with the first possible dataset with a second datasetincluding values representative of predictive regimen parameters relatedto a second subject with one or more similar or dissimilar physicalattributes; one or more instructions 2940 that when executed on the atleast one computing device cause the at least one computing device todetermine from the comparison at least one frozen particle compositiontreatment regimen for the first subject; and at least one generatedoutput optionally based on the determination; one or more instructions2950 that when executed on the at least one computing device cause theat least one computing device to access the first possible dataset inresponse to the first input; one or more instructions 2960 that whenexecuted on the at least one computing device cause the at least onecomputing device to generate the first possible dataset in response tothe first input; one or more instructions 2970 that when executed on theat least one computing device cause the at least one computing device todetermine a graphical illustration of the possible dataset; or one ormore instructions 3000 that when executed on the at least one computingdevice cause the at least one computing device to determine a graphicalillustration of the second possible dataset. In at least one embodiment,the treatment regimen includes at least one of cellular or tissueremoval, cellular or tissue ablation, debridement, delivery of at leastone therapeutic agent, cleaning one or more wounds, removing materialfrom at least one biological tissue, or removing material from at leastone blood vessel 3005. In at least one nitrogen, carbon dioxide,hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine, oxygen,air, argon, polyethylene glycol, acetone, ethyl acetate, dimethylsulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether 3008.

In at least one embodiment, the at least one computing device includesone or more desktop computer, workstation computer, computing systemincluding a cluster of processors, a networked computer, a tabletpersonal computer, a laptop computer, a mobile device, a mobiletelephone, or a personal digital assistant computer 3010. In at leastone embodiment, the at least one computing device is configured tocommunicate with a database to access the first possible dataset 3020.In at least one embodiment, the at least one computing device isconfigured to communicate with a frozen particle composition selectingapparatus, a frozen particle composition generating apparatus, or both3030.

As shown in FIGS. 31-32, at least one aspect relates to a system 3100including circuitry 3110 for receiving a first input associated with afirst possible dataset, the first possible dataset including datarepresentative of one or more measurements relating to one or morephysical attributes of a first subject; circuitry 3120 for comparing avalue associated with the first possible dataset with a second datasetincluding values representative of predictive regimen parameters relatedto a second subject with one or more similar or dissimilar physicalattributes; circuitry 3125 for determining from the comparison at leastone frozen particle composition treatment regimen for the first subject;circuitry 3128 for selecting at least one of quality or quantity relatedto one or more frozen particle compositions, method of administration ofone or more frozen particle compositions, administration location of oneor more frozen particle compositions, content of one or more frozenparticle compositions, timing of administration of one or more frozenparticle compositions, decrease in physical dimension of one or morefrozen particle compositions or time interval between at least twodeliveries with one or more frozen particle compositions.

In at least one embodiment, the system includes circuitry 3130 fordetermining from the comparison at least one frozen particle compositiontreatment regimen for the first subject; and circuitry 3140 forproviding output information optionally based on the comparison. In atleast one embodiment, the circuitry for receiving a first inputassociated with a first possible dataset includes circuitry 3200 forreceiving one or more measurements relating to one or more physicalattributes including at least one of height; weight; body mass index;age; presence or absence of at least one disease or condition; species;ethnicity; race; allergies; gender; thickness of epidermis; thickness ofdermis; thickness of stratum corneum; keratin deposition; collagendeposition; blood vessel condition; skin condition; hair or furcondition; muscle condition; tissue condition; organ condition; nervecondition; brain condition; presence or absence of at least onebiological, chemical, or therapeutic agent in the subject; pregnancystatus; lactation status; genetic profile; medical history; proteomicprofile; partial or whole genetic sequence; partial or whole proteomicsequence; medical history; lymph condition, or blood condition.

In at least one embodiment, the system includes circuitry 3210 forselecting the combination of at least two parameters selected fromquality or quantity related to one or more frozen particle compositions,method of administration of one or more frozen particle compositions,administration location of one or more frozen particle compositions,content of one or more frozen particle compositions, timing ofadministration of one or more frozen particle compositions, decrease ina physical dimension of one or more frozen particle compositions, ortime interval between at least two administrations or deliveries withone or more frozen particle compositions.

In at least one embodiment, the system includes circuitry 3220 forselecting the combination of at least two parameters selected fromquality or quantity related to one or more frozen particle compositions,method of administration of one or more frozen particle compositions,administration location of one or more frozen particle compositions,content of one or more frozen particle compositions, timing ofadministration of one or more frozen particle compositions, decrease ina physical dimension of one or more frozen particle compositions, ortime interval between at least two administrations with one or morefrozen particle compositions.

In at least one embodiment, the system includes circuitry 3230 forselecting at least one of a clinical outcome; secondary effects relatedto the treatment; disease stage; longevity; or vaccinationadministration. In at least one embodiment, the clinical outcome 3240includes a positive clinical outcome or a negative clinical outcome. Inat least one embodiment, the clinical outcome includes one or moreadverse effect, failure to attain a clinical endpoint of a clinicaltrial, failing to attain a beneficial effect, or measurement of at leastone biochemical, biological or physiological parameter 3250.

FIGS. 33-35 illustrate a partial view of a system 3300 including atleast one computer program 3310 configured with a computer-readablemedium, for use with at least one computer system and wherein thecomputer program includes a plurality of instructions including but notlimited to one or more instructions 3320 for determining at least onecomparison between information regarding at least one aspect of cellularor tissue abrasion or ablation of at least one biological tissue of atleast one subject and information regarding at least one clinicaloutcome following receipt by the at least one subject of at least onefrozen particle composition. In at least one embodiment, the systemincludes one or more instructions 3330 for determining at least onestatistical correlation. In at least one embodiment, the system includesone or more instructions 3340 for counting the occurrence of at leastone clinical outcome. In at least one embodiment, information regardingat least one aspect of cellular or tissue abrasion or ablation includesinformation 3350 regarding quantity of cells or tissue removed ordestroyed; information 3360 regarding at least one dimension ofcellular, tissue or other material removal or destruction; information3370 regarding at least one of depth, width, or breadth of cellularremoval or destruction; or information 3380 regarding two or moresubjects with one or more common attributes. In at least one embodiment,the information regarding at least one aspect of cellular or tissueabrasion or ablation includes information 3400 regarding at least onecellular or tissue source, including information 3410 regarding at leastone abnormal cellular or tissue source or information 3420 regarding atleast one type of cell or tissue.

In at least one embodiment, the at least one frozen particle compositionor therapeutic composition includes at least one of polyethylene glycol,acetone, ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol,tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, aceticacid, benzene, carbon tetrachloride, acetonitrile, hexane, methylenechloride, carboxylic acid, saline, Ringer's solution, lactated Ringer'ssolution, Hartmann's solution, acetated Ringer's solution, phosphatebuffered solution, TRIS-buffered saline solution, Hank's balanced saltsolution, Earle's balanced salt solution, standard saline citrate,HEPES-buffered saline, dextrose, glucose, or diethyl ether 3430. In atleast one embodiment, at least one frozen particle composition includesat least one major dimension of approximately one decimeter or less,approximately one centimeter or less, approximately one millimeter orless, approximately one micrometer or less, approximately one nanometeror less, or any value therebetween 3440. In at least one embodiment, theat least one frozen particle composition includes one or morereinforcement agents 3450. In at least one embodiment, the at least onefrozen particle composition includes one or more explosive materials3460.

In at least one embodiment, the receipt by the at least one subject ofat least one frozen particle composition or therapeutic composition ispursuant to at least one clinical trial 3500. In at least oneembodiment, the system further comprises one or more instructions fordetermining at least one comparison before the delivery oradministration of the at least one frozen particle composition ortherapeutic composition to at least one subject 3510.

In at least one embodiment, the system includes one or more instructionsfor creating at least one inclusion criterion and at least one exclusioncriterion for a clinical trial involving the at least one frozenparticle composition or therapeutic composition 3520. In at least oneembodiment, the system further comprises one or more instructions forsuggesting the inclusion of one or more of the at least one subject inat least one clinical trial 3530. In certain instances, multiplesubjects from multiple clinical trials are included.

In at least one embodiment, the system further includes one or moreinstructions for suggesting the exclusion of one or more of the at leastone subject in at least one clinical trial 3540. In at least oneembodiment, the system includes one or more instructions for using oneor more of the at least one comparison to predict at least one clinicaloutcome regarding at least one second subject 3550. In at least oneembodiment, the at least one second subject has not received the atleast one frozen particle composition or therapeutic composition 3560.In at least one embodiment, the system includes predicting at least oneclinical outcome involving the at least one second subject, wherein theat least one second subject is a plurality of people; and segregatingsubject identifiers associated with the plurality of people in referenceto the predicted at least one clinical outcome 3570. In at least oneembodiment, the at least one second subject is a plurality of people;and the system further comprises determining the eligibility of the atleast one second subject for the at least one clinical trial 3580.

As indicated in FIG. 36, at least one aspect relates to a system 3600that includes at least one computer program 3610, configured with acomputer-readable medium, for use with at least one computer system andwherein the computer program includes a plurality of instructionsincluding but not limited to one or more instructions 3620 for comparinginformation regarding at least one aspect of cellular or tissue abrasionor ablation of at least one biological tissue of at least one subjectand information regarding at least one frozen particle compositioninvolving the at least one biological tissue of at least one subject;and one or more instructions 3630 for applying one or more comparisonsto information regarding at least one aspect of cellular or tissueabrasion or ablation regarding a plurality of people. In at least oneembodiment, one or more instructions 3640 for segregating subjectidentifiers associated with the plurality of people in reference to atleast one of the one or more applied comparisons. In at least oneembodiment, the information regarding at least one aspect of cellular ortissue abrasion or ablation includes information 3650 regarding quantityof cells or tissue removed or destroyed; information 3660 regarding atleast one dimension of cellular, tissue or other material removal ordestruction; or information 3670 regarding at least one of depth, width,or breadth of cellular removal or destruction. In at least oneembodiment, the system includes one or more instructions 3680 forsegregating individual identifiers associated with the plurality ofpeople in reference to at least one characteristic shared by two or moresubjects of the plurality of people.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, it will beunderstood by those within the art that each function and/or operationwithin such block diagrams, flowcharts, or examples can be implemented,individually and/or collectively, by a wide range of hardware, software,firmware, or virtually any combination thereof. In one embodiment,several portions of the subject matter described herein may beimplemented via Application Specific Integrated Circuits (ASICs), FieldProgrammable Gate Arrays (FPGAs), digital signal processors (DSPs), orother integrated formats. However, those skilled in the art willrecognize that some aspects of the embodiments disclosed herein, inwhole or in part, can be equivalently implemented in integratedcircuits, as one or more computer programs running on one or morecomputers (e.g., as one or more programs running on one or more computersystems), as one or more programs running on one or more processors(e.g., as one or more programs running on one or more microprocessors),as firmware, or as virtually any combination thereof, and that designingthe circuitry and/or writing the code for the software and or firmwarewould be well within the skill of one of skill in the art in light ofthis disclosure. In addition, those skilled in the art will appreciatethat the mechanisms of the subject matter described herein are capableof being distributed as a program product in a variety of forms, andthat an illustrative embodiment of the subject matter described hereinapplies regardless of the particular type of signal bearing medium usedto actually carry out the distribution. Examples of a signal bearingmedium include, but are not limited to, the following: a recordable typemedium such as a floppy disk, a hard disk drive, a Compact Disc (CD), aDigital Video Disk (DVD), a digital tape, a computer memory, etc.; and atransmission type medium such as a digital and/or an analogcommunication medium (e.g., a fiber optic cable, a waveguide, a wiredcommunications link, a wireless communication link (e.g., transmitter,receiver, transmission logic, reception logic, etc.), etc.).

For any of the various aspects and embodiments disclosed herein, one ormore kits may be developed with the components described herein. In atleast one embodiment, a kit includes one or more frozen particles asdescribed herein. In at least one embodiment, a kit includes one or morefrozen particles and at least one therapeutic agent as disclosed herein.In at least one embodiment, a kit includes one or more frozen particlesand one or more reinforcement agents. In at least one embodiment, a kitincludes one or more frozen particles and one or more explosivematerials.

EXAMPLES Example 1 Compositions and Methods of Making Frozen Particles

Frozen particles suitable for various embodiments described herein maybe produced by controlling the pressure and temperature of hydrogenoxide that is introduced as a liquid, gas or frozen. Frozen particles,including frozen hydrogen oxide ice Ic, are produced by cooling smallhydrogen oxide droplets (˜6 μm diameter) below −38° C. (See e.g.,Murray, et al., Phys. Chem. Chem. Phys. vol. 8, pp.186-192 (2006), whichis incorporated herein by reference). Emulsions of 30-40% by weight ofdistilled and de-ionized hydrogen oxide in paraffin oil (FisherScientific) are agitated to produce hydrogen oxide droplets of meandiameters ranging from 5 to 35 μm as determined by optical microscopy.The droplets are cooled to −100° C. at a rate of 10° C./min by using acryostat cooled with liquid nitrogen and containing a heater andtemperature controller. Freezing liquid droplets with a median diameterof 5.6 μm or smaller can provide approximately 80% frozen ice Ic andapproximately 20% frozen ice Ih. Following the procedures of Murray etal, selective production of ice Ic in pellet form produces quantitiessuitable for use in various embodiments described herein.

Frozen particles generated in this manner are utilized for abrasion ofat least one biological tissue, including but not limited to skin. Thefrozen particle composition is administered to at least one biologicaltissue by, for example, accelerating, ejecting, or propelling the frozenparticles by way of a carrier gas under pressure (e.g., air, carbondioxide, nitrogen) through a tube, or other device directed toward atleast one biological tissue, such as skin. Microdermabrasion,microscissuining, or other surface abrasion techniques are carried outin a similar fashion.

Example 2 Compositions and Methods of Making Frozen Particles

Frozen particles, including frozen hydrogen oxide ice Ic, are producedby depositing hydrogen oxide vapor onto a copper plate held at lowtemperatures in vacuo. Purified (deionized) hydrogen oxide is added to avessel at approximately 25° C. and the hydrogen oxide vapor is condensedonto a metal plate held at approximately −196° C. in vacuo. Thedeposited amorphous ice is heated (at 10° C./min) to approximately −93°C. and is converted to crystalline cubic ice (ice Ic). Ice Ic is stablewhen stored under liquid nitrogen (See e.g., Johari, et al., J. Phys.Chem, vol. 94, pp. 1212-1214 (1990), which is incorporated herein byreference). An example of an apparatus that is used to produce frozenhydrogen oxide ice Ic is described in Hallbrucker et al (J. Phys. Chem.,vol. 93, pp. 4986-4990 (1989), which is incorporated herein byreference).

Example 3 Compositions and Methods of Making Frozen Particles

Frozen hydrogen oxide ice Ic particles are produced from small hydrogenoxide droplets in an example of a “pelletizer” apparatus similar tothose described by, for example, U.S. Pat. No. 4,617,064; U.S. Pat. No.6,306,119, which are incorporated herein by reference. Frozen hydrogenoxide ice Ic particles are formed by spraying hydrogen oxide droplets ofthe desired size into a cooling chamber filled with a cold inert gasmaintained at the desired temperature, for example, nitrogen gasmaintained at approximately −100° C. to promote formation of ice Ic.Spray droplet size is maintained by variation of nozzle/orifice size andhydrogen oxide pressure to yield droplet diameters ranging fromnanometers to centimeters. Frozen hydrogen oxide ice Ic, ice Ih,amorphous low density ice, amorphous high density ice, and other formsare produced by controlling the temperature and pressure of the coolingchamber. Cubic hydrogen oxide ice Ic particles are formed in a step-wiseprocess, by maintaining the chamber at a very low temperature(approximately −196° C.) with increased pressure, which first promotesformation of amorphous hydrogen oxide ice. Next, the chamber is heatedto approximately −93° C., which results in transformation to cubichydrogen oxide ice (ice Ic) particles.

The hydrogen oxide ice particles are propelled into a delivery system(such as tubing and nozzle) by nitrogen gas under pressure. The deliverysystem is maintained at the appropriate temperature for preservation ofthe hydrogen oxide particle structure, (e.g., approximately −93° C. forice Ic structure).

Example 4 Compositions and Methods of Making Frozen Carbon DioxideParticles

Carbon dioxide frozen particles are produced from small carbon dioxidedroplets in a “pelletizer” similar to those described by, for example,U.S. Pat. No. 4,617,064; and U.S. Pat. No. 6,306,119; each of which isincorporated herein by reference. Carbon dioxide frozen particles areformed by spraying liquid carbon dioxide droplets into a cooling chambermaintained at low temperatures (e.g., approximately −100° C.). Dropletsize is regulated by varying nozzle or orifice size, and pressure.Carbon dioxide droplet diameters range, for example, from nanometers tocentimeters. The frozen carbon dioxide particles are propelled into adelivery system (e.g., tubing and nozzle) by carrier gas, (e.g., air ornitrogen) under pressure. The carbon dioxide particles are maintainedwhile in the delivery system at the appropriate temperature, (e.g.,approximately −100° C.). Frozen carbon dioxide particles sublimate, ortransition to a gas phase, at approximately −78.5° C. and 1 atmpressure.

Example 5 Compositions and Methods of Making Frozen DMSO Particles

Dimethyl sulfoxide (DMSO) frozen particles are produced from DMSOdroplets, for example, in a “pelletizer” apparatus similar to thosedescribed by, for example, U.S. Pat. No. 4,617,064; U.S. Pat. No.6,306,119, which are incorporated herein by reference. DMSO frozenparticles are formed from spraying liquid DMSO droplets of the desiredsize into a cooling chamber that is maintained at low temperature, forexample, less than approximately 18.5° C. Droplet size is regulated byvarying nozzle or orifice size, and pressure, with compressed air as acarrier gas. Droplet size can be regulated by varying nozzle or orificesize, and DMSO pressure. DMSO droplet diameters range, for example, fromnanometers to centimeters. The DMSO frozen particles are propelled by acarrier gas (e.g., air or nitrogen) under pressure to enter a deliverysystem (e.g., tubing and nozzle). In order to preserve DMSO particlestructure, the delivery system is maintained at low temperature (e.g.,less than approximately 18.5° C.).

Example 6 Methods of Assessment or Selection of Frozen Particles

According to various embodiments described herein, at least one frozenparticle is made by lowering the temperature of liquid droplets of aselected material. Droplet and particle sizes are measured by imaging aspray or particle stream upon a background screen. The background screenis illuminated with a short pulse of light, for example, from aninfrared laser beam (at approximately 805 run), which is capable ofpulsing at frequencies of approximately 1000 Hz.

A digital camera captures high resolution images of the droplets orparticles. High-speed, real-time particle sizing software analyses theimages to assess the diameter distribution for the particles and todetermine the shape. The diameter of each droplet is determinedautomatically by referencing the number of dark pixels in the dropletimage to the pixel area of a calibration circle. Droplet diametersbetween approximately 100 μm (±3.2%) and approximately 2000 μm (±0.03%)were measured with 95% confidence (See e.g., Ireland et al., 6thASME-JSME Thermal Engineering Joint Conference (2003), which isincorporated herein by reference). Instruments, computer programs andprotocols for measuring particle and droplet size are available, forexample, from Oxford Lasers, Shirley, Mass. (e.g., world wide web atoxfordlasers.com, which is incorporated herein by reference).

Example 7 Methods of Assessment or Selection of Frozen Particles

According to various embodiments described herein, at least one frozenparticle is made by lowering the temperature of liquid droplets of aselected material. Droplet and particle sizes are measured by laserdiffraction. Laser diffraction based particle size analysis relies onparticles passing through a laser beam and scattering light at an anglethat is directly related to their size. As particle size decreases, theobserved scattering angle increases logarithmically. Scatteringintensity is also dependent on particle size, and decreases withdecreasing particle volume. Thus, large particles scatter light atnarrow angles with high intensity whereas small particles scatter atwider angles but with low intensity. Laser diffraction is used for thenon-destructive analysis of wet or dry samples, to measure particles inthe size range 0.02 to 2000 micrometers (e.g., world wide web atchemie.de/articles/e/61205/, which is incorporated herein by reference).A laser diffraction instrument, protocols and analysis software areavailable, for example, from Malvern Instruments Ltd. (Malvern,Worcestershire, WR14 1XZ United Kingdom).

Example 8 Compositions and Methods of Making Frozen Particles Includinga Reinforcement Agent

One or more reinforcement agents are added to the frozen particlesduring the formation process. Among other things, reinforcement agentscan increase the strength of frozen particles (e.g., increase themodulus of rupture of ice) and decrease the deformation of frozenparticles (e.g., decrease the beam deflection of ice). As indicated inTable A below, glass fibers present at 9% (wt./vol.), for example,increase the modulus of rupture of ice by approximately 7-fold relativeto ice derived from unreinforced hydrogen oxide ice (See e.g., Kingery,Science, vol. 134, pp.164-168 (1960), which is incorporated herein byreference).

TABLE A Strength of fresh ice with sawdust and Fiberglass, respectively,added. Additions were % wt./vol. (Kingery, Ibid). Modulus of rupture(kg/cm²) Addition (%) Sawdust (−17° C.) Fiberglass (−20° C.) 0 22.5 24.10.8 22.7 24.0 2.5 35 65.4 9.0 60 161 14.0 66.7 N/A

As indicated in FIG. 5, the beam deflection is less than 0.005 inchesfor hydrogen oxide ice that is reinforced with approximately 9.0% glassfibers and increases over time for hydrogen oxide ice that is reinforcedwith approximately 0.8% glass fibers (Kingery, Ibid). Furthermore,hydrogen oxide ice with approximately 9% (w/v) of glass fibers is notdeformed over 23 hours under an applied force of approximately 24.5in.lbs. As described in Kingery, et al, and as indicated in FIG. 5, beamdeflection of hydrogen oxide ice with approximately 0.8% glass fibers isapproximately 0.16 inches after 23 hours under 25.3 in.lbs. of force.Likewise, as indicated in FIG. 5, and according to Kingery et al,hydrogen oxide ice without reinforcement agents is deformedapproximately 0.05 inches after 4 hours under approximately 26.6 in.lbs.of force. Additionally, aluminum and silica carbonate particles can bemixed at various volume fractions and co-milled under an argonatmosphere to produce nanocrystalline composites as reinforcement agentsfor frozen particle compositions. (See e.g., Kamrani, et al., PowderMet. vol. 50, pp. 276-282(7) (2007), which is incorporated herein byreference).

Example 9 Compositions and Methods of Making Frozen Particles

Frozen particles (e.g., carbon dioxide, DMSO, gelatin) are reinforced byincorporating one or more reinforcement agents, including but notlimited to silica beads, fiberglass, polyethylene glycol, kaolin, orwood fibers.

Silica beads approximately 1 micrometer in diameter are mixed withhydrogen oxide at approximately 0° C. to make volume fractions includingthe approximate ranges, but not limited to, 0, 0.004, 0.04, 0.15, 0.29,0.49 and 0.63 volume fraction. The volume fractions, or one or moreparticular volume fraction, are frozen in, for example, a cylindricalmold, at low temperatures (e.g., approximately −10° C.). Unconfinedcoaxial compression tests are used to determine the maximum stress (alsoknown as the failure point) of the one or more frozen particles atdefined temperatures and strain rates (See e.g., Yasui et al, Geophys.Res. Lett., vol. 35, L12206, (2008), which is incorporated herein byreference).

As indicated in FIG. 6, maximum stress values (MPa) increase formixtures with an increased volume fraction of silica beads relative tothe maximum stress for unreinforced hydrogen oxide ice. (See e.g., Yasuiet al, Ibid.) φ=silica volume fraction

The strength of specific frozen particles is altered by varying thecomposition of frozen particle mixtures containing one or morereinforcement agents. For example, Table B indicates the frozen particlestrength of frozen particles including hydrogen oxide, DMSO, carbondioxide, and gelatin, which contain at least one reinforcement agent. Asindicated, the reinforced frozen particles exhibited increased strengthcompared to their unreinforced counterparts. As indicated in Table B,frozen particles containing at least one reinforcement agent at thevolume fractions shown in the table displayed maximal strength incompression tests. (See also, FIGS. 5 and 6, as well as Table A hereinfor hydrogen oxide frozen particle strength).

TABLE B Frozen particles and reinforcement agents leading to increasedparticle strength Particle Base Fiber Glass Saw Dust Silica Beads PEGKaolin Ice 0.15* 0.14 0.63 ND 0.15 DMSO 0.15 0.14 0.63 ND 0.15 carbon0.15 0.14 0.63 ND 0.15 dioxide gelatin 0.15 0.14 0.63 ND 0.15 Volumefraction for reinforcement agents in frozen particle base materials isgiven. ND = Not Determined. (Yasui, et al.)

Example 10 Vaccine Compositions and Methods of Making Frozen Particles

As described herein, immunization of a subject with a vaccine isaccomplished by way of introduction of the vaccine through, for example,subcutaneous, transcutaneous or intramuscular administration. (See e.g.,Berzofsky et al, Nat. Rev. Immunol. vol. 1, pp. 209-219, (2001), whichis incorporated herein by reference). Non-limiting examples of frozenparticle vaccines are described herein, and include one or moreimmunogens. The immunogen therapeutic compositions are made, forexample, in solution or as a solid in suspension created from bufferedsolutions (e.g., phosphate, citrate, lactate, pyruvate or an organicacid buffer) that optimize the stability and immunogenicity of thevaccine.

Storage stability of vaccines depends upon many factors, includingvaccine formulation and storage temperature. For example, an influenzasubunit vaccine formulated with trehalose, and Hepes buffered saline, isstable at room temperature for approximately 26 weeks (See e.g., Amorijet al, Pharm. Res. vol. 25, pp.1256-1273 (2008), which is incorporatedherein by reference).

Vaccines with adjuvants such as: N-acetylmuramyl-l-alanyl-d-isoglutamine, also called muramyl dipeptide (MDP) ormonophosphoryl lipid A (MPL) elicit enhanced cellular and humoralimmunity (See e.g., Aguilar et al Vaccine vol. 25, pp. 3752-62 (2007),which is incorporated herein by reference).

One or more hydrogen oxide frozen particle vaccine compositions,including, for example, one or more buffers, one or more immunogens(e.g., viral protein subunits) and one or more adjuvants, as a solutionor suspension, are made by spraying the compositions through an orificeor nozzle. Each vaccine composition is propelled by a pressurized gas(e.g., compressed air) into a cooling chamber maintained at, forexample, approximately −40° C.

The vaccine composition is delivered to at least one biological tissueof a subject, for example, by propelling the particles via a carrier gasunder pressure (e.g., air, carbon dioxide, nitrogen) through a tubedirected toward at least one biological tissue (including but notlimited to vascular, lymphatic, lymph node, epidermal, subcutaneous,intramuscular, oral, nasal, pulmonary, intraperitoneal or rectaltissue).

Alternatively, the vaccine composition is delivered to at least onebiological tissue of a subject, for example, by first forming the frozenparticle vaccine compositions through spraying composition droplets intoa cryogen bath (e.g., liquid nitrogen). The frozen particle compositionsare subsequently delivered to at least one biological tissue by flashboiling liquid nitrogen, and propelling the frozen particle compositionsthrough a tube or barrel, for example, to at least one biological tissueof a subject.

Frozen particle vaccine compositions containing one or morereinforcement agents (e.g., silica beads) and of the appropriate sizeand shape (e.g., bullet, spheroid, high aspect ratio shape) penetratethe at least one biological tissue when propelled to high velocity by acarrier gas. In one non-limiting example, a vaccine compositionapproximately 20-70 μm in size penetrates the epidermis when thecomposition is accelerated to high speed with a powder jet injector(PowerJect, PowerJect Pharmaceuticals) (Amorij et al, Ibid.).

Example 11 Vaccine Compositions and Methods of Making Frozen Particles

Frozen particle vaccine compositions containing multiple immunogens, forexample, toxoids (chemically modified toxins) from bacteria such asClostridium tetani, Cornybacterium diphtheriae or Bordetella pertussis,stimulate immunity to multiple bacteria or toxins in a single vaccinecomposition.

Alternatively, multiple distinct immunogens, proteins, or peptides thatare derived from a single pathogen are combined in a single frozenparticle vaccine composition that immunizes a subject against apathogenic virus or bacteria that mutates frequently. For example,multiple hemagglutinin or neuraminidase proteins, (e.g., H1N1, H3N2)from different viral strains (e.g., A/New Caledonia/H1N1, orA/Wellington/H3N2) or viral species of influenza (e.g., influenza A orinfluenza B) are combined in a single frozen particle vaccinecomposition and provides immunity to multiple strains or species. (Seee.g., Kamps et al, Influenza Report, pp. 127-149 (2006); world wide webat influenzareport.com/ir/vaccines; each of which is incorporated hereinby reference).

Alternatively, frozen particle vaccine compositions including one ormore immunogens, antigens or proteins (e.g., influenza A/NewCaledonia/(H1N1)) are combined with one or more frozen particle vaccinecompositions containing one or more different antigens (e.g., influenzaB/Shanghai or influenza A/Wellington/(H3N2)). Such a frozen particlevaccine composition combination provides immunity against seasonalvariants of viral pathogens.

In one non-limiting example, combinations of frozen particle vaccinecompositions including specific antigens from selected influenzavariants or strains target a seasonal flu epidemic. (Kamps et al, Ibid.)Combination of frozen particle compositions are made containing one ormore different antigens or epitopes, wherein the one or more differentantigens or epitopes are derived from mutant or variant HIV proteinsthat evolve during HIV infection (See e.g., Berzofsky et al, J. Clin.Inv. vol. 114, pp. 450-462 (2004)). Such combination compositionsimmunize a subject against existing HIV mutants and anticipate theemergence of new HIV mutants or variants.

Alternatively, one or more frozen particle vaccine compositions aredelivered to one or more mucosal tissues (e.g., nasal, oral, rectal,pulmonary) via propulsion using a “pellet gun,” via inhalation, oringestion by a subject. For example, an influenza vaccine lyophilizedand delivered nasally as spherical particles, approximately 26.9 μm(mean diameter), induces mucosal (e.g., nasal IgA response) and systemicimmunity (e.g., serum antibody response) to influenza virus (See e.g.,Garmise et al, AAPS PharmSciTech. vol. 8:E81 (2007); Huang et al,Vaccine. vol. 23(6), pp. 794-801 (2004); each of which is incorporatedherein by reference).

Alternatively, the one or more frozen particle vaccine compositions aredelivered to one or more pulmonary surfaces of the subject viapropulsion by way of a “pellet gun,” by using flash boiled liquidnitrogen as a propellant, or by inhalation. Frozen particle influenzavaccine compositions administered to one or more pulmonary surfaces of asubject elicit mucosal and systemic humoral, as well as cell-mediatedimmune responses to influenza (See e.g., Amorij et al Vaccine. vol. 25,pp. 8707-8717 (2007), which is incorporated herein by reference).

Example 12 Compositions and Methods of Making Frozen Particles

Frozen particle compositions of the appropriate size and shape,including botulinum toxin, an optimal buffer (e.g., Hepes buffer), oneor more stabilizing agents, and one or more reinforcement agents areadministered through the skin of a subject to neuromuscular junctions.Botulinum toxin inhibits acetylcholine release, which blocks synapseformation, and temporarily paralyzes the corresponding musculature.

Frozen particle compositions containing a recommended dose of botulinumtoxin (See e.g., Borodic, U.S. Pat. No. 5,183,462, which is incorporatedherein by reference), and at least one reinforcement agent (e.g.,polymer) are administered to skeletal muscles using a delivery systemderived from inkjet printer technology (See e.g., world wide web aten.wikipedia.org/wiki/Inkjet Printer) that sprays picoliter quantitiesof the frozen particle compositions at high velocity (e.g., 50 m/sec)toward the skin of the subject. Botulinum toxin is typicallyadministered by subcutaneous injection (generally with a 26 gaugehypodermic needle). Botulinum toxin is approved by the FDA for therapyof strabismus (crossed-eyes), blepharospasm (uncontrolled blinking), andother facial nerve disorders including hemifacial spasm. It is alsoapproved for treatment of cervical dystonia and glabellar (frown) lines(See e.g., Jankovic, J. Neurol. Neurosurg. Psychiatry vol. 75, pp.951-957 (2004), which is incorporated herein by reference).

In addition, botulinum toxin is included in the treatment of focal orsegmental dystonia (e.g., oromandibular-facial-lingual dystonia,laryngeal dystonia, limb dystonia). Dystonias are neurological disorderswith repetitive and patterned contractions of muscles that causeabnormal movements and postures. For example, cervical dystonia subjectsare injected with, for example, approximately 100 I.U of botulinumtoxin, distributed over 3-5 injection sites, spaced 5-15 mm apart,across the length of the sternomastoid muscle. (Borodic, Ibid.)

Frozen particle vaccine compositions containing botulinum toxin areadministered to facial muscles that underlie frown lines, wrinkles, and“crow's feet.” For example, botulinum toxin is targeted to: 1) thecorrugator and procerus muscles to treat vertical glabellar eyebrowfurrows; 2) to multiple sites in the frontalis muscle to eliminatehorizontal lines in the forehead; or 3) to the lateral orbicularis oculito treat crow's feet.

Frozen particle compositions containing an optimal dose of botulinumtoxin (e.g., 0.2-0.4 I.U./kg) are administered over the length of aspecific facial muscle (e.g., orbicularis oculi) by use of a deliverysystem with an inkjet nozzle. As described herein, picoliter volumes ofone or more frozen particle compositions are sprayed at a velocity thatachieves a desired or predetermined depth (for example, 5-8 mm; Borodic,Ibid.). The velocity is also altered according to the size, shape, andconstituents of the frozen particle composition.

Example 13 Methods of Administering Frozen Particle TherapeuticCompositions

Frozen hydrogen oxide particles of ice Ic form and at least onetherapeutic agent or at least one diagnostic agent are formulated fortreatment of hematological cancers (e.g., leukemia or lymphoma) or solidtumors (e.g., carcinoma, sarcoma). For example, at least one ofneo-adjuvant therapy, adjuvant therapy, chemotherapy, antibody therapy,or immunotherapy are employed

In one non-limiting embodiment, frozen hydrogen oxide particles are usedfor adjuvant therapy of cancers treated with surgery such as coloncancer, lung cancer, and breast cancer. At least one frozen particlehydrogen oxide therapeutic composition containing one or morereinforcement agents (e.g., silica beads, Kevlar®), one or more buffers,one or more stabilizing agents (e.g., one or more saccharides), and oneor more cancer therapeutic agents (such as one or more chemotherapydrugs, antibodies, biological agents (e.g., antibodies, cytokines orpeptides), or one or more chemotherapeutic agents) are administered toan area proximal to a region of at least one biological tissue where atumor is present or believed to be present. Optionally, resection of atleast a part of a tumor may be performed, with or without additionaladministration of the at least one frozen particle therapeuticcomposition.

The at least one frozen particle therapeutic composition is administeredin such a manner as described herein, that allows for desired depth ofpenetration of the at least one biological tissue. In one embodiment,the at least one frozen particle therapeutic composition is administeredto a depth that allows for at least one of intracellular orintercellular delivery. For example, the at least one frozen particletherapeutic composition is administered to a depth that allows fordelivery to at least one of epithelium, endothelium, vasculature,lymphatic vessels, lymph nodes or mucosa.

Specifically, if metastasis is present or believed to be present in thesubject, administration of the at least one frozen particle therapeuticcomposition is delivered to such region of metastases ormicro-metastases are believed to be present.

Frozen particle hydrogen oxide therapeutic compositions provide as anadjuvant therapy are administered by spraying at least one compositionunder pressure with a carrier gas through a nozzle designed to uniformlydistribute particles over at least one biological tissue at sufficientvelocity to penetrate the tissue exposed during tumor resection.

Advanced colon cancer (e.g., stage II, III) is treated surgically byremoval of sections of colon containing tumor with margins of “normal”colon tissue and often includes removal of associated lymph nodes andmesentery (colectomy). Standard adjuvant therapy following surgery issystemic administration of a combination of chemotherapy drugs (e.g.,5-fluorouracil, leucovorin or oxaliplatin (FOLFOX)), (See e.g., Wolpinet al, CA Cancer J. Clin. vol. 57, pp.168-185 (2007)). Systemic FOLFOXadjuvant therapy is associated with significant toxicities includinggastrointestinal toxicity, neutropenia and neurotoxicity (Wolpin et al,Ibid.). Localized in situ delivery of FOLFOX by administration of frozenparticle therapeutic compositions permits delivery of a lower dose.

Administration of at least one frozen particle hydrogen oxidetherapeutic composition containing at least one therapeutic antibodyincludes, for example, bevacizumab (an anti-vascular endothelial growthfactor) or cetuximab (an anti-epidermal growth factor receptor).Bevacizumab and cetuximab both target the tumor-associated vasculatureand tumor cells in the remaining colon sections and the surroundingtissues, mesentery and lymph nodes. Localized administration oftherapeutic antibodies provides sustained protection from recurrence ofcolon tumors at the site of tumor resection and in the surroundingtissues. (Wolpin et al, Ibid.). Following surgery and adjuvant therapywith one or more frozen particle hydrogen oxide therapeuticcompositions, including at least one of one or more chemotherapy drugs,or one or more antibodies, the remaining colon sections are splicedtogether (i.e. anastomosis) or an artificial orifice (i.e. stoma) isinserted to restore a functional colon.

Example 14 Methods of Administering Frozen Particle TherapeuticCompositions

Frozen particle hydrogen oxide therapeutic compositions including one ormore cancer therapeutics or one or more cancer diagnostics are used totreat cancers in distal locations from the primary tumor or initialtumor site treated with surgery or radiation. For example, colon cancercells often metastasize to the liver ((Wolpin et al, Ibid.). At the timeof surgical resection of colon cancer tumors, one or more frozenparticle hydrogen oxide therapeutic compositions including at least onecancer therapeutic, such as one or more cytotoxic drugs (e.g.,fluouracil), antibodies (e.g., cetuximab), radioisotopes conjugated toantibodies (e.g., ¹³¹I-cetuximab), or one or more mixtures of at leastone cytotoxic drug and at least one biological-based therapeutic agentare administered to the liver and surrounding tissues.

Administration of the at least one frozen particle hydrogen oxidetherapeutic composition is accomplished by traditional surgery orlaparoscopic surgery that allows access to the liver (or other organs tobe treated). Administration of at least one frozen particle hydrogenoxide therapeutic composition directly to the liver and the surroundingvasculature allows for intracellular or intercellular penetration andrelease of at least one anti-cancer therapeutic for treatment of anyexisting or suspected colon cancer mestastases or micro-metastases.

As described herein, the at least one frozen particle hydrogen oxidetherapeutic composition including one or more cancer therapeutics areadministered by way of a spraying device. Such a spraying deviceincludes an insulated tube and nozzle, as well as a valve that controlsthe flow of particles. In the case of traditional surgery for tumor ortissue resection, the at least one frozen particle hydrogen oxidetherapeutic composition is sprayed directly onto the target tissue ortissues. Whereas in the case of laparoscopic surgery for tumor or tissueresection, the at least one frozen particle hydrogen oxide therapeuticcomposition is sprayed through a trocar (a hollow tube approximately 10millimeters in diameter).

In certain spraying devices, the at least one frozen particle hydrogenoxide therapeutic composition is administered by way of a carrier gas.The depth of penetration by the at least one therapeutic composition iscontrolled by regulating the carrier gas pressure as well as theconsequent particle velocity. The at least one therapeutic compositionoptionally includes one or more tracer agents or is deliveredsimultaneously with one or more tracer agents. Some non-limitingexamples of tracer agents include dyes, stains or fluorescent compoundsthat mark the tissue area sprayed. The one or more tracer agents canoptionally monitor or provide feedback as to the quantity or quality (inthe case of multiple therapeutic compositions administeredsimultaneously or over time) of the at least one therapeutic compositionadministered to a specific site.

In at least one embodiment, the at least one frozen particle hydrogenoxide therapeutic composition including at least one cancer therapeuticfurther includes hematoxylin and eosin stains mixed at a known ratio(e.g., 1:10). Alternatively, a batch of the at least one frozen particlehydrogen oxide therapeutic composition is administered in a mixture orin separate applications frozen particles including hematoxylin andeosin stains. Staining of tissues is visualized by inspection with a lowpower microscope (e.g., dissection microscope) or with a laparoscope,which allows for assessment of the relative quantity or quality of theat least one therapeutic composition administered to the tissue.Staining of the tissues further provides a guide as to the region thatreceived the at least one therapeutic composition.

Example 15 Methods of Administering Frozen Particle TherapeuticCompositions

Frozen particle hydrogen oxide therapeutic compositions including carbondioxide and at least one cancer therapeutic are administered to at leastone tumor or tissue suspected of being cancerous. Upon administration,the frozen particle hydrogen oxide therapeutic compositions penetrateone or more tumor cells, warm to ambient temperature, and undergo rapidsublimation and gaseous expansion of the carbon dioxide. This rapidreaction produces a small explosion that destroys at least one tumorcell as well as one or more adjacent cells. In addition, administrationof the frozen particle therapeutic compositions at low temperatures(e.g., lower than approximately −78.5° C., which is the approximatesublimation temperature for carbon dioxide at 1 atm pressure), freezescells and tissues, causing tumor cell death (See e.g., Vergnon et al,Eur. Respir. J. vol. 28 pp. 200-218 (2006); incorporated herein byreference).

Alternatively, carbon dioxide gas is entrapped in frozen particles byplacing the liquid phase (e.g., hydrogen oxide) under high pressure inthe presence of carbon dioxide gas. (See e.g., U.S. Pat. Nos. 4,289,794;4,289,790; 4,262,029; 5,439,698, each of which is incorporated herein byreference). Administration of the at least one therapeutic compositionis conducted as described herein. In at least one embodiment, the use ofa tube and nozzle is used that sprays the frozen particle therapeuticcompositions under pressure in a carrier gas (e.g., carbon dioxide,nitrogen). Administration of the at least one therapeutic composition iscarried out as an adjuvant therapy in conjunction with tumor resection,or as an alternative when tumor resection is not favored. For examplelung cancer tumors are generally inoperable when such tumors areadjacent to airways, or infiltrate central airways including thetrachea, main stem bronchi or multiple lung lobes. Additionally,subjects with compromised respiration (e.g., those with lung disease,heart disease or advanced age) are generally not candidates for surgery(See e.g., Spiro et al, Amer. J. Respir. Crit. Care Med., vol. 172, pp.523-529 (2005); which is incorporated herein by reference).

Carbon dioxide frozen particle therapeutic compositions including one ormore chemotherapeutic drugs (e.g., cisplatin, docetaxel, vinorelbine),targeted drugs (e.g., gefitnib, erlotnib), or biological-based agents(e.g., cetuximab, panitumumab, bevacizumab) are administered directlyonto lung cancer tumors. Administration is conducted via endoluminalbronchoscopy or by video-assisted thoracoscopy by means of an insulatedtube and nozzle integral to the endoscopic device. Frozen particlecomposition velocities and spray rate are controlled by a valve betweenthe spray head and the cooling chamber of the “pelletizer.” (See e.g.,U.S. Pat. Nos. 6,306,119, or 6,764,493, each of which is incorporatedherein by reference). Precise localization and administration of thefrozen particle therapeutic compositions are accomplished bybronchoscopy and endoscopy with fluoroscopy used to mark the field(s) ofinterest.

Methods for endoscopic targeting of tumors are described, for example,in Huber et al (Chest vol. 107, pp. 463-470 (1995); which isincorporated herein by reference). Moreover, computed tomography,magnetic resonance imaging, positron emission tomography or othertechniques are used to locate lung cancer tumors.

Frozen particle therapeutic composition administration by usingendoscopic procedures or as an adjuvant therapy in conjunction withtraditional surgery is used for various regions of existing or potentialcarcinogenesis, including mediastinal lymph nodes, vasculature, chestwall and other thoracic sites.

Alternatively, frozen particle therapeutic compositions are deliveredduring traditional surgery for lung cancer and used to treat inoperabletumors remaining following lobectomy, wedge resection, andpneumonectomy, as well as to treat margins of lobe, wedge or lungexcisions to reduce recurrence of lung cancer (See e.g., theworldwideweb at en.wikipedia.org/wiki/Lung cancer#Surgery; which isincorporated herein by reference). Without wishing to be bound by anyparticular theory, frozen particle carbon dioxide therapeuticcompositions maintained at approximately −80° C. while administered totumors rapidly freeze the tumor cells leading to formation of icecrystals in tumor cells that destroy cell organelles (e.g.,mitochondria) leading to death of the tumor cells. (Vergnon et al,Ibid.)

Similarly, frozen particle therapeutic compositions containing at leastone radioactive element deliver radiation to lung cancer tumor cells.One non-limiting example utilizes frozen particle therapeuticcompositions including ¹⁹²Iridium for irradiating lung tumors thatobstruct major airways. Administration of the frozen particletherapeutic compositions is conducted using an endoscope and a wire toplace the radioactive compositions in at least one lung tumor. Withoutwishing to be bound to any theory, tumor cell irradiation results insingle-stranded DNA breaks that induce apoptosis and reduce rates ofcell division (Vergnon et, Ibid.).

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent to those skilled inthe art that, based upon the teachings herein, changes and modificationsmay be made without departing from the subject matter described hereinand its broader aspects and, therefore, the appended claims are toencompass within their scope all such changes and modifications as arewithin the true spirit and scope of the subject matter described herein.It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to claims containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that typically a disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms unless context dictates otherwise. For example, the phrase “Aor B” will be typically understood to include the possibilities of “A”or “B” or “A and B.”

With respect to the appended claims, those skilled in the art willappreciate that recited operations therein may generally be performed inany order. Also, although various operational flows are presented in asequence(s), it should be understood that the various operations may beperformed in other orders than those which are illustrated, or may beperformed concurrently. Examples of such alternate orderings may includeoverlapping, interleaved, interrupted, reordered, incremental,preparatory, supplemental, simultaneous, reverse, or other variantorderings, unless context dictates otherwise. Furthermore, terms like“responsive to,” “related to,” or other past-tense adjectives aregenerally not intended to exclude such variants, unless context dictatesotherwise.

All publications and patent applications cited in this specification areincorporated herein by reference to the extent not inconsistent with thedescription herein and for all purposes as if each individualpublication or patent application were specifically and individuallyindicated to be incorporated by reference for all purposes.

1. A therapeutic composition, comprising: one or more frozen solutionparticles including at least one therapeutic agent; wherein the one ormore frozen solution particles have at least one major dimension ofapproximately one centimeter or less, approximately one millimeter orless, approximately one micrometer or less, approximately one nanometeror less, or any value therebetween.
 2. The therapeutic composition ofclaim 1, wherein the therapeutic composition exists at about 30° C.,about 20° C., about 10° C., about 5° C., about 0° C., about −10° C.about −20° C., about −30° C., about −40° C., about −50° C., about −60°C., about −70° C., about −75° C., about −80° C., about −85° C., about−90° C., about −95° C., about −100° C., about −120° C., about −150° C.,about −180° C., about −200° C., about −220° C., about −250° C., or anyvalue less than or therebetween.
 3. The therapeutic composition of claim1, wherein the therapeutic composition is in at least one crystalline oramorphous phase.
 4. The therapeutic composition of claim 1, wherein theat least one major dimension includes at least one of the radius,diameter, length, width, height, or perimeter.
 5. The therapeuticcomposition of claim 1, wherein the at least one therapeutic agentincludes at least one of an organic or inorganic small molecule,clathrate or caged compound, protocell, coacervate, microsphere,proteinoid, laminate, helical rod, liposome, macroscopic tube, niosome,sphingosome, toroid, vesicular tube, vesicle, small unilamellar vesicle,large unilamellar vesicle, large multilamellar vesicle, multivesicularvesicle, lipid layer, lipid bilayer, micelle, organelle, cell, membrane,nucleic acid, peptide, polypeptide, protein, glycopeptide, glycolipid,sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan, lipid,sphingolipid, glycosphingolipid, carbohydrate, metalloprotein,proteoglycan, chromosome, nucleus, acid, base, buffer, protic solvent,aprotic solvent, nitric oxide, nitric oxide synthase, amino acid,micelle, polymer, co-polymer, or piloxymer.
 6. The therapeuticcomposition of claim 1, wherein the at least one therapeutic agentincludes at least one of an anti-tumor agent, antimicrobial agent,anti-viral agent, analgesic, antiseptic, anesthetic, diagnostic agent,anti-inflammatory agent, vaccine, cell growth inhibitor, cell growthpromoter, immunogen, antigen, radioactive agent, apoptotic promotingfactor, angiogenic factor, anti-angiogenic factor, hormone, vitamin,mineral, nutraceutical, cytokine, chemokine, probiotic, coagulant,anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer,smooth muscle cell activator, epinephrine, adrenaline, neurotoxin,neuro-muscular toxin, Botulinum toxin type A, microbial cell orcomponent thereof, or virus orrotoxin, neuro-muscular toxin, microbialcell or component thereof, or virus or component thereof.
 7. Thetherapeutic composition of claim 6, wherein the antimicrobial agentincludes at least one of an anti-fungal agent, antibiotic agent,anti-parasitic agent, or anti-worm agent.
 8. The therapeutic compositionof claim 6, wherein the at least one anti-tumor agent includes one ormore of an alkylating agent, antimetabolite, anthracycline, plantalkaloid, topoisomerase inhibitor, monoclonal antibody, or tyrosinekinase inhibitor.
 9. The therapeutic composition of claim 8, wherein theat least one plant alkaloid includes paclitaxel.
 10. The therapeuticcomposition of claim 1, further comprising one or more of nitrogen,argon, helium, air, oxygen, neon, xenon, krypton, chlorine, bromine,carbon dioxide, polyethylene glycol, acetone, ethyl acetate, dimethylsulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide,perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formicacid, hydrogen fluoride, ammonia, acetic acid, benzene, carbontetrachloride, acetonitrile, hexane, methylene chloride, carboxylicacid, saline, Ringer's solution, lactated Ringer's solution, Hartmann'ssolution, acetated Ringer's solution, phosphate buffered solution,TRIS-buffered saline solution, Hank's balanced salt solution, Earle'sbalanced salt solution, standard saline citrate, HEPES-buffered saline,dextrose, glucose, or diethyl ether.
 11. The therapeutic composition ofclaim 1, wherein the at least one therapeutic agent includes one or moreof a prodrug or precursor compound.
 12. The therapeutic composition ofclaim 11, wherein the at least one therapeutic agent is activated bydelivery of the therapeutic composition to at least one biologicaltissue.
 13. The therapeutic composition of claim 1, wherein the one ormore frozen particles approximate the shape of at least one of a sphere,bullet, flechette, cone, needle, arrow, spear, diamond, pyramid,cylinder, minie ball, shuttlecock, spiral, bell, pear, crystal, cube,spheroid, tetrahedron, crescent, or high aspect ratio shape.
 14. Thetherapeutic composition of claim 1, wherein the at least one therapeuticagent resides in one or more distinct regions of the one or more frozenparticles.
 15. The therapeutic composition of claim 1, wherein the oneor more frozen particles include a plurality of frozen particles thatare approximately uniform in size, shape, weight, or density.
 16. Thetherapeutic composition of claim 1, wherein the therapeutic compositionincludes at least one of a solid, liquid, or gas.
 17. The therapeuticcomposition of claim 1, wherein the therapeutic composition includes oneor more of a suspension, mixture, solution, clathrate, sol, colloid,emulsion, microemulsion, aerosol, ointment, capsule, powder, tablet,suppository, cream, device, paste, liniment, lotion, ampule, elixir,spray, suspension, syrup, tincture, detection material, polymer,biopolymer, buffer, adjuvant, diluent, lubricant, disintegration agent,suspending agent, solvent, calorimetric agent, glidant, anti-adherent,anti-static agent, surfactant, plasticizer, emulsifying agent, flavor,gum, sweetener, coating, binder, filler, compression aid, encapsulationaid, preservative, granulation agent, spheronization agent, stabilizer,adhesive, pigment, sorbent, nanoparticle, or gel.
 18. The therapeuticcomposition of claim 1, further comprising one or more reinforcementagents.
 19. The therapeutic composition of claim 18, wherein the one ormore reinforcement agents include at least one of a natural, artificial,or synthetic agent.
 20. The therapeutic composition of claim 18, whereinthe one or more reinforcement agents include at least one of a plate,fiber, or spheroid.
 21. The therapeutic composition of claim 18, whereinthe one or more reinforcement agents include at least one of polyaramid,vinylester matrix, metal, ceramic, fiberglass, cellulose, broad carbide,aromatic polyamide, nylon, silk, rayon, acetate, modacrylic, olefin,acrylic, polyester, aromatic polyester, poly-lactic acid, vinyon, saran,spandex, vinalon, aromatic nylon, vinylidene chloride, modal,polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performancepolyethylene, polypyridobenzimidazole, vectran, acrylonitrile rubber,glass, copper, iron, steel, sodium, potassium, calcium, zinc, manganese,carbon, magnesium, silicon, silica, frozen hydrogen oxide ice, plantmatter, animal matter, or mineral matter.
 22. The therapeuticcomposition of claim 18, wherein the one or more reinforcement agentsare located at least on the surface or beneath the surface of theparticle.
 23. The therapeutic composition of claim 18, wherein the oneor more reinforcement agents are located within the particle.
 24. Thetherapeutic composition of claim 1, further comprising at least onepolymer, biopolymer, nanoparticle, or detection material.
 25. Thetherapeutic composition of claim 24, wherein the detection materialincludes at least one electronic identification device.
 26. Thetherapeutic composition of claim 25, wherein the at least one electronicidentification device includes at least one radio frequencyidentification device.
 27. The therapeutic composition of claim 24,wherein the detection material includes at least one radioactiveelement.
 28. The therapeutic composition of claim 27, wherein the atleast one radioactive element includes one or more of ³²P, ³⁵S, ¹³C,¹³¹I, ¹⁹¹Ir, ¹⁹²Ir, ¹⁹³Ir, ²⁰¹Tl, or ³H.
 29. The therapeutic compositionof claim 24, wherein the detection material includes at least onecolorimetric substance.
 30. The therapeutic composition of claim 29,wherein the at least one calorimetric substance includes one or more ofan inorganic, organic, biological, natural, artificial, or syntheticsubstance.
 31. The therapeutic composition of claim 29, wherein the atleast one colorimetric substance includes one or more of a dye, pigment,or light-emitting substance.
 32. The therapeutic composition of claim31, wherein the light-emitting substance includes at least one of afluorescent substance, phosphorescent substance, or quantum dot.
 33. Thetherapeutic composition of claim 29, wherein the at least onecolorimetric substance is biocompatible.
 34. The therapeutic compositionof claim 24, wherein the detection material includes at least one of adiamagnetic particle, ferromagnetic particle, paramagnetic particle,super paramagnetic contrast agent, or other magnetic particle.
 35. Thetherapeutic composition of claim 1, formulated to be administered by oneor more of topical delivery, oral delivery, enteral delivery, mucosaldelivery, percutaneous delivery, or parenteral delivery.
 36. Thetherapeutic composition of claim 1, wherein parenteral delivery includesat least one of intravenous delivery, intra-arterial delivery,intracardiac delivery, subcutaneous delivery, intraperitoneal delivery,or intramuscular delivery.
 37. The therapeutic composition of claim 1,formulated to be administered by high velocity impact.
 38. Thetherapeutic composition of claim 1, formulated to be administered by oneor more devices.
 39. The therapeutic composition of claim 1, furthercomprising at least one pharmaceutically-acceptable carrier orexcipient.
 40. The therapeutic composition of claim 1, furthercomprising one or more explosive materials. 41-152. (canceled)